Content uploaded by Olubunmi Abosede Wintola
Author content
All content in this area was uploaded by Olubunmi Abosede Wintola on Feb 13, 2015
Content may be subject to copyright.
Afolayan and Wintola Afr J Tradit Complement Altern Med. (2014) 11(3):248-258
http://dx.doi.org/10.4314/ajtcam.v11i3.35
248
DIETARY SUPPLEMENTS IN THE MANAGEMENT OF HYPERTENSION AND DIABETES - AREVIEW
Anthony Jide Afolayan1*and Olubunmi Abosede Wintola1
1Medicinal Plant and Economic Development Research Centre, Department of Botany, University of Fort Hare, Alice
5700, South Africa.
* Email: Aafolayan @ufh.ac.za
Abstract
Background: The use of alternative therapies like herbs and dietary supplements is very common among hypertensive and diabetic patients all over
the globe. Hypertension is a silent disease that causes increase in cardiovascular, cerebrovascular, renal morbidity and mortality whereas diabetic
complications cause heart attack, stroke, blindness and kidney disease. These are serious and chronic metabolic disorders that have a significant
impact on the health, quality of life, and life expectancy of patients, as well as on the health care systems. Orthodox drugs used for the treatment of
hypertension and diabetes produce side effects such as headache, nausea, vomiting, stomach pain, constipation, diarrhea, weakness, fatigue and
erectile dysfunction. The need for considering alternate therapies in the formof dietary supplements known to promote good health, having little or no
side effects therefore arises.
Materials and methods: This review was carried out using comprehensive and systematic literature reports on the concurrent use of dietary
supplements in the management of diabetes and hypertension. Empirical searches were conducted using Google scholar (http:// scholar. google.com),
and Science Direct (http://www.science direct.com). In addition to these databases, the University database was also used. Searches were also
undertaken using keyword combinations such as dietary supplements and the names of the diseases in question.
Result and Discussion: This review chronicled the therapeutic values of vitamins, minerals, amino acids, fruits, vegetables, herbs and other botanicals
used as dietary supplements. Results show that these supplements provided better and safe substitutes to toxic and expensive conventional drugs.
Generally dietary supplements are free from major side effects, readily available and affordable. It is envisaged that the use of dietary supplement will
promote good health and improve the status of hypertensive and diabetic patients.
Conclusion: Medical doctors are therefore encouraged to incorporate dietary supplements into the regimen employed for hypertension and diabetes
management.
Keywords: Blood pressure, blood glucose, botanicals, minerals, vitamins
Introduction
The practice of using nature as pharmacy dates back to antecedent/s and continues till date as many of the medications currently in use are
derived from plants. Dietary supplements are food products, extracts or concentrates that are intended to supplement diets because they contain certain
dietary ingredients such as vitamins, minerals, herbs, and amino acids (Halsad, 2003). They are usually found in many forms including tablet, capsule,
powder, liquid, bar, soft-gel and gel-cap.
Dietary supplements are generally regarded as classes of foods not drugs. This is because like foods, most dietary supplements are not
screened for safety and effectiveness following their removal from the regulatory authority of the Federal Food, Drug and Cosmetic Act of 1958. This
prevents dietary supplements labels from assertions showing their intended ability to treat, diagnose, mitigate, prevent or cure diseases (DSHEA,
1994). The line between permissible and impermissible health claims for supplements is not always clear to the consumer, who naturally may
misunderstand the apparent bounty of medicinal-sounding risk-free benefits. However, while many supplements may be beneficial, they are not
without risks. Generally, several claims have been put forward regarding the beneficial attributes of dietary supplements including prevention of acne,
reduction of fats, low cholesterol content, rich fibre content, and the promotion of healthy skin (DSHEA, 1994).
Dietary supplements occur in different forms ranging from vitamins, minerals, amino acids and botanicals. Vitamins are organic compounds
that cannot be synthesized by the body, but are necessary for its proper functioning. There are two types of vitamins namely; fat soluble and water
soluble vitamins. Fat soluble vitamins are A, D, E and K which can be stored in the body for future use. Vitamins B and C are water soluble that
cannot be stored by the body and therefore need to be replenished regularly through diet in order to avoid deficiencies which can interfere with normal
metabolic processes and cause severe illness (Bellow and More, 2012). For instance, pellagra and beriberi diseases result from niacin (vitamin B3),
and thiamin (vitamin B1) deficiencies while scurvy is a disorder arising from ascorbic acid (vitamin C), deficiency (Beckman et al., 2001; Gaede et
al., 2001; Pemberton, 2006).
Minerals are inorganic elements derived from soil and water which are absorbed by plants and eaten by animals. Some of these minerals are required
in large amounts by the body e.g. calcium for bone development. Others like chromium, copper, iron, selenium and zinc often called trace minerals are
needed in very small amounts. These minerals are chemical elements required by all living organisms along with carbon, hydrogen, nitrogen and
oxygen for proper growth and development (Soetan et al., 2010).
Amino acids are the building blocks of proteins and they can be categorized into three groups namely indispensable (essential), conditionally
indispensable and dispensable (non-essential). Indispensable amino acids must be consumed in the diet while conditionally indispensable amino acids
can be synthesized by human body under most conditions but may require dietary supplementation under certain patho-physiological conditions such
as catabolic stress or neonatal prematurity (Morris et al., 2002). Five amino acids are dispensable, meaning that they can be synthesized from other
amino acids or complex metabolites (Engelhart et al. 2002).
Other dietary supplements include metabolites and extracts. Metabolites are substances that are produced by metabolic actions or are
necessary for metabolic processes while extracts are substances usually biologically active ingredients of plant or animal tissues prepared by the use of
solvents to separate the substance from the original material. A herbal remedy is a plant or plant part (root, flower, leaf, and fruit), that is used for its
medicinal or therapeutic properties (Awoyemi et al., 2012). The potency of herbal products varies depending on each plant’s growing conditions, level
of maturity when harvested and the processes used to dry and store each ingredient.
Afolayan and Wintola Afr J Tradit Complement Altern Med. (2014) 11(3):248-258
http://dx.doi.org/10.4314/ajtcam.v11i3.35
249
The popularity and increase in the use of dietary supplements have been reported by the media, government agencies and published studies
in medical journals (De Smet, 2000; Litovitz et al., 2001; Spencer, 2004; Wise, 2004). Reports showed significant difference/s in dietary supplement
usage by age, with higher prevalence in older age groups for all supplements and for single ingredient vitamins/minerals. There is also a significant
difference in supplement use by sex, with women having the upper hand than men for all supplements except herbs and botanicals. A significant
difference also exists with respect to race/ethnicity, with higher use amongst whites than any other groups for all supplements including
multivitamins/minerals. Household income as well as the level of education of users also shows some level of significance difference for all
supplement, multivitamins/multi-minerals and herbs users (Timbo et al., 2006).
Methodology
This review was carried out by a comprehensive and systematic literature search on the concurrent use of dietary supplements in the
management of diabetes and hypertension. Empirical researches were conducted using Google scholar (http:// scholar. google.com) and Science Direct
(http://www.science direct.com). In addition to these databases, the University of Fort Hare’s online database were also used. Significant inquiries
were also made using keyword combinations such as dietary supplements and the names of the diseases in question.
Specific disease and types of dietary supplements used in its management
Dietary supplements used in the management of Hypertension includes cod liver oil, garlic, Co-enzyme Q10, beta glucan, lipoic acid, whole
grains, vitamins E, B6, C, potassium, magnesium, sodium, polyphenol, botanicals and vanadium.
Dietary supplements used in the management of Diabetes includes Alpha-lipoic, chromium, omega 3 fatty acids, polyphenols, garlic, magnesium, co-
enzyme Q10, vanadium, folic acid, selenium, vitamins B6, C and E, zinc and copper.
Hypertension
Hypertension is a highly prevalent chronic medical condition in which blood pressure in the arteries is elevated (Tabassum and Ahmad,
2011). It is a global health burden affecting both developed and developing countries (Kearney et al., 2005). The condition is becoming an
increasingly common problem and this may be attributed to the increasing longevity and prevalence of contributing factors such as obesity, physical
inactivity and unhealthy diets (Singh et al., 2000; Yusuf et al., 2001). It is a silent disease, which if untreated or sub-optimally controlled, could lead to
increase in cardiovascular, cerebrovascular as well as renal morbidity and mortality.
The proportion of global disease burden attributed to hypertension is substantially affecting 32% of men and 30% of women aged 16 and
above in England (WHO, 2003; Huisman et al., 2004). The high prevalence of hypertension globally contributes to the present anticipated pandemic
of cardiovascular diseases (CVD), which is of particular concern in developing countries (Kearney et al., 2005). The control of hypertension, together
with other associated risk factors such as dyslipidemia and diabetes mellitus, constitute the ideal approach to primary prevention of atherosclerotic
disease, and remains a major challenge for communities. The trend towards comprehensive cardiovascular risk factor management is the
internationally accepted model of care (WHO, 2002).
Hypertension is more prevalent in men than in women and even more in those of low socio-economic status though menopause tends to
decrease this difference (Carretero and Oparil, 2000). This gender disparity is common in hypertension (Du et al., 2006). Before menopause, blood
pressure (BP) is significantly lower in women than in age-matched men. However, the incidence/s of hypertension increases dramatically in women
following menopause, eventually approximating the incidence in men (Kotchen et al., 1982; Spence, 1996). Although the mechanism underlying this
increase is unknown, the loss of oestrogen traditionally has been considered the primary factor (Kearney et al., 2005).
Dietary supplements used in the management of hypertension
Dietary interventions have been shown to reduce the occurrence of high blood pressure (Appel et al., 2006). In the United States, the
combined use of herbal supplements as home remedies for the management of hypertension was put at 48% (Mansoor, 2001). Furthermore, in a
survey performed within a primary care setting in Alabama, 41% of patients were taking nutritional supplements and 26% were taking herbal products
(Phillips and Osborne, 2000). In another report by Winslow and Kroll (1998), up to 90% of hypertensive patients take either over-the-counter
medications or supplements depending on the definitions used.
Studies in other patient populations including those suffering from hypertension have also shown a significant prevalence of supplements,
herbs and other alternative therapy use (Gulla and Singer, 2000; Cappuccio et al., 2001). It is therefore a common practice among patients attending a
medical care setting to use dietary supplements. Unfortunately, most patients do not reveal the use of such treatments to their health care providers
(Gulla and Singer, 2000). Common dietary supplements used in the management of hypertension, their health benefits and limitations are presented in
Table 1. Dietary folate and plasma ascorbic acid have been found to be inversely associated with blood pressure in observational studies (Forman et
al., 2005). However, intervention trials with vitamin C yielded inconsistent results (Ness et al., 1997). While in two small trials, folic acid was
effective at lowering blood pressure, the finding of a lower risk of elevated blood pressure in the multiple supplement groups suggests that there was a
relationship between these nutrients and blood pressure (van Dijk et al., 2001; Mangoni et al., 2002).
Some studies have reported the concurrent use of dietary supplements and conventional antihypertensive drugs. For example, Co-enzyme
Q10 has been reported to exhibit significant reduction of systolic blood pressure (SBP), and diastolic blood pressure (DBP), when added to
conventional antihypertensive drugs (Singh et al., 1999; Rasmussen et al., 2012). Similarly, the systolic blood pressure (SBP) and diastolic blood
pressure (DBP) were reported to have decreased by 6 mm Hg and 5 mmHg respectively in a trial where hypertensive men received fish oil
(eicosapentaenoic acid, docosahexaenoic acid) for 4 months followed by a 2 month reassessment period (Prisco et al., 1998).
Diabetes
Diabetes, borrowed from a Greek word meaning siphon, is a metabolic disorder marked by high levels of blood glucose resulting from
Afolayan and Wintola Afr J Tradit Complement Altern Med. (2014) 11(3):248-258
http://dx.doi.org/10.4314/ajtcam.v11i3.35
250
defects in insulin production, insulin action or both which can lead to serious complications and premature death (Afolayan and Sunmonu, 2010).
However, people with the condition, working together with their support network and their health care providers can take steps to control the disease
and lower the risk of complications.
Diabetes mellitus is a serious disease that has a significant impact on the health, quality of life and life expectancy of patients as well as the
health care system (Dey et al., 2002). It is a disorder affecting the metabolism of carbohydrates, fats, proteins and electrolytes in the body leading to
acute, sub-acute and chronic complications (Rang et al., 1991). Hyperglycemia, ketoacidosis and non ketotic syndromes are some of the complications
of acute diabetes (Knentz and Nattras, 1991), while thirst, polyuria, visual blurriness, weight loss and lack of energy are experienced in sub-acute
diabetes incidence (Kumar and Clark, 2002). Chronic hyperglycemia complication causes bonding of a protein or lipid molecules with a sugar
molecule (glycation) which may eventually affect the eye, kidney, nervesand arteries (Sharma, 1993; Afolayan and Sunmonu, 2010).
Three main forms of diabetes were recognized by the world Health Organization; these are type 1, type 2, and gestational diabetes (WHO,
1999). These three forms of diabetes showed common symptoms but differs in their causes, diagnosis, population distribution and treatment. The
causes of diabetes are due to the beta cells of the pancreas being unable to produce sufficient insulin to prevent hyperglycemia (Rother, 2007). Type 1,
diabetes previously called insulin-dependent diabetes mellitus (IDDM), or juvenile-onset diabetes is usually due to auto-immune destruction of the
pancreatic beta cells which produce insulin. It develops when the body's immune system destroys pancreatic beta cells, the only cells in the body that
produce the hormone insulin that regulates blood glucose (Holt, 2004). People with type 1 diabetes must have insulin delivered by injection or a pump.
It usually strikes children and young adults, although disease onset can occur at any age. Type 2 previously called non-insulin-dependent diabetes
mellitus (NIDDM), usually begins as insulin resistance, a disorder in which the cells do not use insulin properly (Holt, 2004). It is characterized by
tissue-wide insulin resistance and varies widely; it sometimes progresses to loss of beta cell function. As the need for insulin rises, the pancreas
gradually loses its ability to produce insulin. Type 2, diabetes is associated with older age, obesity, family history of diabetes, history of gestational
diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity. Gestational diabetes occurs during pregnancy, it is similar to type 2,
diabetes, which involves insulin resistance. The hormones of pregnancy cause insulin resistance in those women genetically predisposed to developing
this condition.
The World Health Organization (WHO) estimated diabetes in adults to be around 173 million, and about two-thirds of these patients live in
developing countries (Wild et al., 2004; Sunmonu and Afolayan, 2013). The prevalence of diabetes is on the increase worldwide, and this is still
expected to increase by 5.4% in 2025 (Moller and Flier, 1991; Sunmonu and Afolayan, 2013). Women suffer from diabetes in both developed and
developing countries. Approximately, 2.1 million women die of diabetes each year in the world, making diabetes the ninth leading cause of death
among women (IDF, 2011). Increase in sedentary lifestyle, consumption of energy-rich diet and obesity are some of the factors causing the rise in the
number of diabetics. According to the American Diabetes Association (1997), Asia and Africa are regions with the greatest potential where diabetics
could rise to two or threefold above the present level (Sunmonu and Afolayan, 2010).
Dietary supplements used in the management of diabetes
The management of diabetic condition has advanced considerably over the past 50 years. Today, people living with diabetes are able to use
advanced equipment and treatments such as electronic monitors which gives accurate readings of their glucose levels. There are also insulin pumps
about the size of a beeper, strapped to a belt which gives measured insulin injections under the skin. Despite this development, dietary supplements are
still used to a very large extent in the management of diabetes (Table 2). Some dietary supplements that have been studied in clinical trials include
alpha-lipoic acid, chromium and omega-3 fatty acids (Martin et al., 2006).
Alpha-lipoic acid (ALA), also known as lipoic acid or thioctic acid and acts as an antioxidant substance that protects against cell damage.
ALA has been researched for its effect on insulin sensitivity, glucose metabolism and diabetic neuropathy (Jacob et al., 1996). Diabetic patients also
take chromium in an effort to improve their blood glucose control. Chromium supplementation in diabetics has been researched but not with some
controversies. While some researchers have found benefits, others have indicated little or no benefits (Cefalu and Hu, 2004). Therefore, additional
high-quality research is needed to prove its efficacy. Omega-3 fatty acids are another class of compound that has been researched for their effect on
controlling glucose and reducing heart disease risk in people with Type 2, diabetes. Studies showed that omega-3 fatty acids lower triglycerides, but
do not affect blood glucose control, total cholesterol or HDL (good), cholesterol in people with diabetes (De Luis et al., 2009).
Complementary medicine is mostly used along with conventional medicine while alternative medicine is replacing conventional medicine
(Egede et al., 2002). For example, ALA, Chromium supplements, cinnamon and host of other supplements have proved successful for quite some time
in the treatment for peripheral neuropathy. ALA has been reported to lower blood glucose level even though; there is no evidence that the supplement
prevents neuropathy (Ziegler et al., 1995; Reljanovic et al., 1999). However, chromium supplement on A1C, glucose, and insulin levels have shown
little effect in a trial among diabetes and non diabetic patients, other studies have shown some benefit on these same markers in subjects who were
chromium deficient (Althius et al., 2002). Similar reports was reported where participant received 1, 3, or 6 g of cinnamon daily for 40 days to have
lowered the blood glucose levels of participants from 18 to 29%. There was further reduction in the glucose level for up to 20 days for the participants
who consumed the least quantity (1g) of the supplement even after the discontinuation of its use (Khan et al., 2003). Despite insufficient data on
supplement safety and effectiveness, the fact remains that people with diabetes do and will continue to use dietary supplements.
Reasons for the use of dietary supplements in the management of hypertension and diabetes
Several reasons can be attributed to the upsurge in the use of dietary supplements for the management of diseases. Diabetes and
hypertension represent huge financial cost to the government and affected individuals, which is predicted to increase over the next 20 years. Not
everyone can afford the latest technology and advancements in the treatment of these diseases; dietary supplements and pharmacological interventions
are therefore necessary (Bastaki, 2005).
Another important factor is lack of response and unwanted side effects arising from the use of conventional treatments which have forced many
patients to explore dietary supplements as alternative therapy (Halat and Dennehy, 2003). The properties of dietary supplements used to treat
hypertension and diabetic neuropathy are well described (Halat and Dennehy, 2003; Gupta and Guptha, 2010) Comparisons of these supplements with
regard to dosages, frequencies and adverse effects described in medical literatures help with selection of the most appropriate supplements for
individual patient. Majority of hypertensive patients (especially those with mild elevated blood pressure), claim they obtained little or no benefit from
drug therapy and that the risks of some orthodox drugs far outweigh the benefits (Mansoor, 2001). Therefore, diet and other non-pharmacological
approaches represent a safer approach to treating diabetes and hypertension with the added benefit of reduced cost (Halat and Dennehy, 2003).
Afolayan and Wintola Afr J Tradit Complement Altern Med. (2014) 11(3):248-258
http://dx.doi.org/10.4314/ajtcam.v11i3.35
251
Table 1: Common dietary supplements used in the management of hypertension
S/no Dietary
supplement Nutrients/ food
sources Form found Target organ/cell Health benefits Limitations Reference
1. Cod liver oil Vitamin A, D, and
omega-3 fatty acids.
Fish oils, flax seed,
primrose, borage
and flaxseed oils.
Herring haddock,
Atlantic salmon, trout,
tuna, cod and mackerel.
Cardiovascular
system. Reduces cardio
metabolic risk factors,
protects sudden cardiac
death after myocardial
infraction, reduces
raised plasma
triglycerides, reduces
blood pressure and
ameliorates atherogenic
effects.
High doses required for
reduction of blood
pressure may have side
effects.
Warner, 2000;
Marchioli et al., 2002;
Hooper et al., 2006;
Apel et al., 2006;
Abeywardena and
Patten, 2011; Trofimiuk
and Braszko, 2011.
2. Garlic Gamma glutamyl
peptides, flavonol
magnesium, ajoenes
phosphorus,
adenosine, allicin
and sulphur
Allium sativum, aglio,
ail, Da-suan,
Knoblauch, La-juan,
rustic treacle, stinking
rose
Cardiovascular
system. Reduces cardiovascular
diseases by lowering
blood pressure and
increases levels of
antioxidant enzymes.
Inhibits platelet
aggregation which may
prolong bleeding time.
Mohamadi et al., 2000;
Weiss, 2000;
Mansoor, 2001.
3. Coenzyme Q-
10 B vitamins; B6,
B12, niacin and
folic acid. Fatty
fish, organ meats
and peanut.
Reduced or oxidized
form of CoQ10 in
dry powder capsules
dispersed in oil,
surfactants and
emulsifiers such as
lecithin and polysorbate
80 to improve
absorption.
Heart, lung and liver Strengthens heart
muscle and improves a
variety of heart
conditions.
Low level compromises
myocardial energy
generation leading to
“energy starvation” of the
myocardium, considered
to be a
pathogenic mechanism of
chronic heart failure
(CHF).
Mohamadi et al., 2000;
Weiss, 2000;
Mansoor, 2001.
4. Beta glucan Sorghum, rye,
maize, triticale,
wheat, rice, seaweed
and mushrooms.
Oat and barley
bran. Heart Immune enhancer and
cholesterol-lowering
effect.
Delay stomach emptying. Mohamadi et al., 2000;
Weiss, 2000;
Mansoor, 2001.
5. Lipoic acid Liver, spinach,
broccoli and potato. Lipoic acid in tablet and
capsule. Nerve cell, kidney,
heart and liver. Lowers blood pressure
in persons with
hypertension.
Pregnant women or
nursing mothers should
avoid lipoic acid
supplements at
pharmacologic doses.
Mohamadi et al., 2000;
Weiss, 2000;
Mansoor, 2001.
6. Whole grains Brown rice, wheat,
barley, rye, maize. Oat meal, polenta,
wheat pasta, wheat
bread, corn meal.
Heart and liver Reduces systolic and
diastolic pressures
along with mean arterial
pressure (MAP).
Intake of three servings a
day must be ensured for
positive result.
Anderson et al., 2000.
7. (i) Potassium Fruits and
vegetables
such as apricots,
Citrate and chloride. Cell membranes. Reduces blood pressure. Potassium depletion in
normal individuals causes
sodium retention and
Kotchen and McCarron,
1998.
Afolayan and Wintola Afr J Tradit Complement Altern Med. (2014) 11(3):248-258
http://dx.doi.org/10.4314/ajtcam.v11i3.35
252
bananas, tomatoes
and carrots. increased blood pressure.
(ii)
Magnesium Fat or fibre (from
fruits, vegetables
and cereal grains.
Citrate, stearate and
sulphate forms. Heart and kidney. Inhibits platelet
dependent thrombosis.
Inadequate levels may
cause loose stool in
sensitive individuals.
Touyz, 1991; Burgess et
al., 1999.
(iii) Sodium Fat or fibre from
fruits, vegetables
and cereal grains.
Additive in commercial
processed foods. Heart and blood
vessels. Moderate intake
reduces mean arterial
pressure as well as
morbidity and
mortality.
Excess sodium in the diet
can lead to or complicate
high blood pressure.
McCarron, 1997
Burgess et al., 1999;
Kotchen and McCarron,
1998.
8. Vitamin E Vegetable oil,
sunflower nuts,
avocado, carrot,
peanut, almonds,
hazelnuts.
Alpha – Tocopherol Heart, brain, lung,
and muscle Reduces elevated blood
pressure caused by
excess endogenous
aldehydes in insulin
resistance hypertension.
Large doses of α-
tocopherol inhibits normal
blood coagulation.
Jiang et al., 2001;
Vasdev et al., 2002.
9. Vitamin B6 Brown rice, oats,
wheat germ,
molasses, cereals,
potato, banana,
plum and salmon
fish.
Pyridoxine Jejunum, ileum,
heart. Prevents heart attacks
and nerve damage. Excess doses over long
period of time result into
painful and ultimately
irreversible neurological
problem.
Schaumburg et al.,
1983; Bendich and
Cohen, 1990;
McCormick, 2006.
10. Vitamin C Fruits and
vegetables. Ascorbic acid Blood plasma, brain,
spleen, lung, liver,
kidney and pancreas.
Lowers blood pressure
in persons with
hypertension, helpful
for long term health
maintenance of arteries.
Causes diuretic effect
which gets rid of fluids. Ness et al., 1997;
Vasdev et al., 2002.
11. Polyphenol Fruits and
vegetables, nuts and
their products.
Catechin and
epicatechin. Heart Inhibits oxidation of
low density lipoprotein
(LDL), inhibits platelet
aggregation and
vascular relaxation
through the production
of nitric oxide.
Safety should be carefully
tested in relation to the
disease status of potential
users.
Frankel et al., 1993;
McCarron, 1997;
Dubick and Omaye,
2001; Halsad, 2003;
Carlson et al., 2008.
12. Botanicals Prickly pear, cactus,
Coccinea indica,
Aloe vera,
fenugreek, bitter
melon, Ginseng.
Herbs Liver, bones, skin
and heart. Prevents hypertension
and ulcerative colitis. Lack of dose regimen and
limited research on the
efficacy of these
botanicals.
Merchant and Andre,
2001; Van Breemen et
al., 2007.
13. Vanadium Black pepper,
mushroom, shell
fish parsley, fresh
fruits and
vegetables.
Chelate and sulphates. Muscles, liver, heart
and body fluids. Lowers blood pressure. GI irritation and tissue
accumulation, uncertain
long term safety profile.
Bhanot et al., 1994a;
Bhanot et al., 1994b
Cohen et al., 1995;
Goldfine et al., 1995;
Boden et al., 1996;;
Preuss et al., 1998.
Afolayan and Wintola Afr J Tradit Complement Altern Med. (2014) 11(3):248-258
http://dx.doi.org/10.4314/ajtcam.v11i3.35
253
Table 2: Common dietary supplements used in the management of diabetes
S/no Dietary
supplement Nutrients/ food source Form found Target organ/cell Health benefits Limitations Reference
1. Alpha-lipoic
acid Liver, spinach, broccoli
and potato. lipoic acid in tablet
and capsule. Nerve cell, kidney
and liver. Prevents cell damage,
improves the body’s ability
to use insulin.
May lower blood
sugar too much. Jacob et al., 1995; 1996;
Konrad et al., 1999.
2. Chromium Trace element,
meat, whole grain
products, some fruits,
vegetables and spices.
Capsule and tablets
sold as chromium
picolinate, chromium
chloride, chromium
nicotinate.
Pancreas Keeps pancreas working
well and lowers blood sugar
levels.
Lower doses are
safer as high doses
can cause kidney
problem.
McCarty, 1999; Althuis et
al., 2002; Cefalu and He,
2004; Balk et al., 2007;
Jellin and Gregory, 2007.
3. Omega- 3fatty
acids Poly unsaturated fatty
acids. Oil, vegetable oil
(canola and soybean),
walnuts, and wheat
germ.
Capsule or oil. Liver and heart. Maintains blood glucose
levels. Safer at low to
moderate doses,
may interfere with
certain medications.
Hartweg et al., 2007;
Hartweg et al., 2008.
4. Polyphenols Tea and dark chocolate. Green tea Vascular tissue Lowers blood glucose
levels by enhancing insulin
action.
Contains caffeine,
which can cause, in
some people,
insomnia, anxiety,
or irritability.
Green tea also has
small amounts of
vitamin K, which
can make
anticoagulant drugs,
such as warfarin,
less effective.
Fukino
et al., 2005;
Ryu
et al., 2006
Collins et al., 2007; Kim
et al., 2007;
Mackenzie et al., 2007;
Potenza et al., 2007.
5. Garlic Allium sativum S-ally cysteine
sulphoxide (SACS).
Pancreas
Reduces fasting blood
glucose and lower serum
cholesterol levels.
Inhibits platelet
Aggregation and
may prolong
bleeding time.
Sheela and Augusti, 1992;
Kaczmar, 1998.
Banerjee and Maulik,
2002.
6. Magnissium Fat or fibre from fruits,
vegetables, cereals and
grain.
Citrate, chloride,
sulphate and stearate. Heart, kidney and
muscle. Improves insulin response
and glucose handling
in the elderly and in type 2
diabetics.
Causes loose stool
in sensitive
individuals.
Begon et al., 2000;
Larsson and Wolk, 2007;
Schulze et al., 2007.
7. Coenzyme Q10 B vitamins i.e. niacin
and folic acid. Fatty
fish, organ meat,
peanuts, spinach.
Oil Heart, liver and
lungs. Improves long-term
glycemic control in type 2
diabetics.
Body stores of Co-
Q10 can be reduced
when used
alongside prescribed
diabetic medications
such as glyburide.
Anderson et al, 2001;
Hodgson et al., 2002;
Bonadkdar and Guarneri,
2005.
8. Vanadium Black pepper,
mushroom , shell fish
parsley, fresh fruits and
vegetables.
Chelate and
sulphates. Muscles, liver and
body fluids. Helps cells of both the liver
and muscles use insulin
more effectively, controls
glucose and insulin
sensitizers.
Adverse reactions of
diarrhea, green
Tongue, nausea,
vomiting and
cramps are reported.
Cusi et al., 2001.
9. Folic Acid Vitamin B9, spinach
Oxidized synthetic
Liver and kidney Along with B12, folic acid
High dosages cause
Salardi et al., 2000.
Afolayan and Wintola Afr J Tradit Complement Altern Med. (2014) 11(3):248-258
http://dx.doi.org/10.4314/ajtcam.v11i3.35
254
broccoli, avocado,
oranges, tomatoes,
banana.
folate tablet form. prevents strokes and loss of
limbs due to diabetic
complications.
neural damage.
10. Selenium Broccoli, raddish,
cabbage, onion, garlic,
cereals, meat,
mushroom, fish , nuts
and egg.
Chelate Small intestine,
kidney Helps take blood sugar into
cells, protects against blood
vessel and nerve damage
from elevated blood sugars.
Low blood selenium
predisposes to
cancer, coronary
heart disease and
diabetes.
Mukherjee et al., 1998;
Stapleton, 2000.
11. Vitamin B6 All bran, brown rice,
oats, molasses, wheat
germ, banana, plum,
fish and salmon.
Pyridoxine Jejunum, ileum Pyridoxine with folic acid,
B12 and B6 helps prevent
diabetic blindness and
vision loss.
Excessive vitamin
B6 produces
painful, disfiguring
dermatological
lesions.
Bendich and Cohen, 1990;
Ellis et al., 1991;
McCormick, 2006.
12. Vitamin C Fruit and vegetables Ascorbic acid Endothelial cells Improves insulin stimulated
glucose metabolism. May raise blood
sugar level. Paolisso et al., 1994;
1995.
13. Vitamin E Vegetable oil,
sunflower, nuts, whole
grain, green leafy
avocado, carrot,
peanuts, almond,
hazelnuts.
Tocopherol Kidney, brain,
muscles, heart and
lung.
Produces a significant
improvement in insulin
mediated glucose
utilization in healthy people
and type-2 diabetics.
Large doses of α-
tocopherol are
known to deplete
plasma and tissue γ-
tocopherol.
Paolisso et al., 1993;
Barbagallo et al., 1999;
Jiang et al., 2001.
14. Zinc Minerals Zinc (picolinate) Immune and
metabolic cells. Assists normal production,
storage and secretion of
insulin, necessary for the
conformational integrity of
insulin, helps blood sugar
get into cells.
Significantly higher
doses may cause
nausea, vomiting,
headache and
drowsiness.
Paolisso et al., 1993;
Barbagallo et al., 1999;
Jiang et al., 2001.
15. Copper Oat, bran, apple,
almond. Copper picolinate Pancreas, blood
vessels and nerves. Protects pancreatic cells,
prevents diabetes-related
damage to blood vessels
and nerves and lowers
blood sugar levels.
Health benefits
impaired by high
intake of zinc.
Johnson et al., 1998;
Sitasawad et al., 2001.
Afolayan and Wintola Afr J Tradit Complement Altern Med. (2014) 11(3):248-258
http://dx.doi.org/10.4314/ajtcam.v11i3.35
255
Shortcomings of dietary supplements
Notwithstanding the popularity and widespread use of dietary supplements, a number of shortcomings have been recorded against them.
Some of the risks involved include allergic reactions, competitive inhibition for absorption of other nutrients and drug-nutrient interactions resulting in
long-term adverse effects. (Palmer and Howland, 2001; Palmer and Betz, 2002). Most of the dietary supplements including herbs and botanicals do
not undergo the same stringent regulatory approval process as drugs. Food and drug laws do not require demonstration of safety and efficacy to
support legal marketing of dietary supplements. There is lack of standardization among brands of supplements and the bioactive ingredients in
products can vary widely (van Breemen et al., 2007). For instance, few clinical trial reports are available to support the use of herbal and botanical
supplements in the prevention or treatment of high blood pressure or heart disease. At a minimum, health care professionals should ask their patients
about the use of herbal products and educate them on the possibility of herb-drug interactions. The active compound of a particular herb may not be
known or if known may not be on the label. Furthermore, the amount of the active substance stated may not be accurate. Quality control measures
vary from company to company and from product to product. Consumers should consider buying from manufacturers that have obtained
Pharmacopeia standards for product purity and content reliability, thus at least ensuring somestandards are followed during manufacture.
Conclusion
Dietary supplements used presently occur in a variety of forms including vitamins, minerals, herbals, botanicals, amino acids and enzymes.
Deficiency in the consumption of some recommended foods requires the use of supplements. This may help ensure adequate amounts of essential
nutrients and help promote optimal health and performance. Scientific evidence supporting the benefits of some dietary supplements is well
established for certain health conditions like hypertension and diabetes. In affected individuals, inadequate nutritional intake of essential vitamins and
minerals may worsen their conditions. Therefore, additional nutrients from supplements can help patients meet their medical needs and requirements.
We envisage that the application of dietary supplements in the management of hypertension and diabetes is an opportunity for health care
professionals to work in partnership with patients to educate and support beneficial self-care behaviors.
Acknowledgments
This research was supported by grants from NRF and Govan Mbeki Research and Development Centre, University of Fort Hare, South
Africa.
References
1. Abeywardena, M.Y., and Patten, G.S. (2011). Role of omega 3 Long chain polyunsaturated fatty acids in reducing cardio-metabolic risk factors. End.
Metabol. and Immune Disorder-Drug Target., 11 (3):232-246.
2. Afolayan, A.J., and Sunmonu, T O. (2010). In vivo studies on Antidiabetic plants used in South Africa Herbal medicine. J. Clin. Biochem. Nutri., 47: 98-106.
3. Althuis, M.D., Jordan, N.E., Ludington, E.A. and Wittes, J.T. (2002). Glucose and insulin responses to dietary chromium supplements: A meta-analysis. Am.
J. Clin. Nutr., 76(1):148-155.
4. American Diabetes Association, “Standards of medical care for patients with diabetes mellitus (position statement),” Diabetes Care, vol. 20, no. 1, pp. 518–
520, 1997.
5. Anderson, J.W., Hanna, T.J., Xuejun, Peng B.S., and Kryscio, R.J. (2000). Whole grain food and heart disease risk. J Ame College of Nutri., 19 (3): 291-299.
6. Anderson, R.A., Evans, M.L., Ellis, G.R., Graham, J., Morris, K., Jackson, S.K., Lewis, M.J., Rees, A., and Frenneaux M.P. (2001). The relationships
between post-prandial lipaemia, endothelialfunction and oxidative stress in healthy individuals and patients with type 2 diabetes. Atherosclerosis., 154: 475-483.
7. Appel, L.J., Brands, M.W., Daniels, S.R., Karanja, N., Elmer, P.J., and Sacks, F.M. (2006). Dietary approaches to prevent and treat hypertension. A scientific
statement from the American Heart Association. Hypertension, 47:296-308.
8. Awoyemi, O.K., Ewa, E.E., Abdulkarim, I.A., and Adepoju AR. (2012). Ethnobotanical assessment of herbal plants in South-Western Nigeria. Acad. Res.
Intern., 2 (3): 50-57.
9. Balk, E.M., Tatsioni, A., Lichtenstein, A.H., Lau, J., and Pittas, A.G. (2007). Effect of chromium supplementation on glucose metabolism and lipids: a
systematic review of randomized controlled trials. Diabetes Care., 30(8):2154-2163.
10. Banerjee, S.K., and Maulik, S.K. (2002). Effect of garlic on cardiovascular disorders: A review. Nutri. Journal., 1: (1):4.
11. Barbagallo, M., Dominguez, L.J., Tagliamonte, M.R., Resnick, L.M., and Paolisso, G. (1999). Effect of vitamin E and glutathione on glucose metabolism:
Role of magnesium. Hyper., 34: 1002-1006.
12. Bastaki, S. (2005). Review: Diabetes mellitus and its treatments. Int. J. Dia Metabol., 13: 111-134.
13. Beckman, J.A., Goldfine, A.B., Gordon, M.B., and Craeger, M.A. (2001). Ascorbate restores endothelium-dependent vasodilation impaired by acute
hyperglycemia in humans. Circulation., 103:1618-1623.
14. Begon, S., Pickering, G., Eschalier, A., and Dubray, C. (2000). Magnesium and MK-801 have a similar effect in two experimental models of neuropathic
pain. Brain. Res., 887:436-439.
15. Bellows, I., and Moore, R. (2012). Water-soluble vitamins: B- complex and vitamin C. Colorado State University, Cooperative Extension fact sheet No.
9.312.
16. Bendich, A., and Cohen, M. (1990). Vitamin B6 safety issues. Annals of New York Academy of Sci., 585:321-30.
17. Bhanot, S., Bryer-Ash, M., Cheung, A., and McNeill, J.H. (1994a). Bis (maltolato) oxovanadium (IV) attenuates hyperinsulinemia and hypertension in
spontaneously hypertensive rats. Diabetes., 43:857-861.
18. Bhanot, S., McNeill, J.H., and Bryer-Ash, M. (1994b) Vanadyl sulfate prevent fructose-induced hyperinsulinemia and hypertension in rats. Hyperten., 23:308-
312.
19. Boden, G., Chen, X., Ruiz, J., van Rossum, G.D.V., and Turco, S. (1996). Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with
non-insulin-dependent diabetes mellitus. Metabol., 45:1130-1135.
20. Bonadkdar, R.A., and Guarneri, E. (2005). Coenzyme Q10. American Family Physician, 72(6):1065-1069.
Afolayan and Wintola Afr J Tradit Complement Altern Med. (2014) 11(3):248-258
http://dx.doi.org/10.4314/ajtcam.v11i3.35
256
21. Burgess, E., Lewanczuk, R., Bolli, P., Chockalingam, A., Cutler, H., Taylor, G., and Hamet P. (1999). Recommendations on potassium, magnesium, and
calcium. Can. Med. Ass., 160: (9) 35-45.
22. Cappuccio, F.P., Duneclift, S.M., Atkinson, R.W., and Cook, D.G. (2001). Use of alternative medicines in a multi-ethnic population. Ethnic and Dis., 11:11-
18.
23. Carlson, S., Peng, N., Prasain, J.K., and Wyss, J.M. (2008). Effects of Botanical dietary supplements on cardiovascular, cognitive and metabolic function in
males and females. Gender Med., 5: 76-90.
24. Carretero, O.A., and Oparil S. (2000). "Essential hypertension. Part I: definition and etiology". Circulation., 101 (3): 329–35.
25. Cefalu, W.T., and Hu, F.B. (2004). Roleof chromium in human health and in diabetes. Diabetes Care, 27:2741-2751.
26. Cohen, N., Halberstasm, M., Slimovitch, P., Shammon, H., and Rosetti, L. (1995). Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in
patients with non-insulin-dependent diabetes mellitus. J. Clin. Invest., 95:2501-2509.
27. Collins, Q.F., Liu, H.Y., Pi, J., Liu, Z., Quon, M.J., and Cao, W. (2007). Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, suppresses hepatic
gluconeogenesis through 5-AMP activated protein kinase. J. Bio. Chem., 282(41):30143-30149.
28. Cusi, K., Cukier, S., DeFronzo, R.A., Torres, M., Puchulu, F.M., and Redondo, J.C. (2001). Vanadyl sulfate improves hepatic and muscle insulin sensitivity
in type 2 diabetes. J. Clin. Endocrinol, Metab., 86: 1410-1417.
29. De Luis, D.A., Conde, R., Aller, R., Izaola, O., Gonzalez Sagrado, M., Perez Castrillon, J.L., Duenas A., and Romero, E. (2009). Effect of omega-3 fatty acids
on cardiovascular risk factors in patients with type 2 diabetes mellitus and hypertriglyceridemia: an open study. Eur. Rev. Med. Pharmacol. Sci., 13: 51-55.
30. De Smet, P.A. (2000). Herbal remedies. New Engl. J. Med., 347:2046-2056.
31. Dey, L., Attele, A.S., and SuYuan, C. (2002). Alternative therapies for type 2 diabetes. Alt. Med. Rev., 7 (1): 45-48.
32. DSHEA. (1994). Dietery supplements Health and Education Act. www.wikipedia accessed on 11/04/2013.
33. Du, X.J., Fang, L., and Kiriazis, H. (2006). Sex dimorphism in cardiac pathophysiology: Experimental findings, hormonal mechanisms, and molecular
mechanisms. Pharmacol. Ther., 111:434-475.
34. Dubick, M., and Omaye, S.T. (2001). Modification of atherogenesis and heart disease by grape wine and tea polyphenols. In: Wildman REC, ed.
Handbook of nutraceuticals and functional foods. Boca Raton, FL: CRC Press, 235-260.
35. Egede, L.E., Ye, X., Zheng, D., and Silverstein, M.D. (2002). The prevalence and pattern of complementary and alternative medicine use in individuals with
diabetes. Dia. Care., 25:324-329.
36. Ellis, J.M., Folkers, K., Minadeo, M., Vanbuskirk, R., Xia, L.J., and Tamagawa H. (1991). A deficiency of vitamin B6 is a plausible molecular basis of the
retinopathy of patients with diabetes mellitus. Biochem. Biophy. Res. Comm., 179: 615-619.
37. Engelhart, M.J., Geerlings, M.I., Ruitenberg, A., van Swieten, J.C., Hofman, A., Witteman, J.C., and Breteler, M.M. (2002). Dietary intake of antioxidants
and risk of Alzheimer disease. J. Am. Med. Ass., 287: 3223-3229.
38. Forman, J.P., Rimm, E.B., Stampfer, M.J., and Curhan, G.C. (2005). Folate intake and the risk of incident hypertension among US women. JAMA., 293:320-
329.
39. Frankel, E.N., Kanner, J., German, J.B., Parks, E., and Kinsella, J.E. (1993). Inhibition of oxidation of human low-density lipoprotein by phenolic substances
in red wine. Lancet., 341:454-457.
40. Fukino, Y., Shimbo, M., Aoki, N., Okubo, T., and Iso, H. (2005). Randomized controlled trial for an effect of green tea consumption on insulin resistance and
inflammation markers. J. Nutr. Sci. Vitaminol., 51(5):335–342.
41. Gaede, P., Poulson, H.E., Parving, H.H., and Pederson, O. (2001). Double-blind, randomised study of the effect of combined treatment with vitamin C and E
on albuminuria in Type 2 diabetic patients. Diabet Med.; 18:756-760.
42. Goldfine, A.B., Simonson, D.C., Folli, F., Patti, M.E., and Kahn, C.R. (1995). Metabolic effects of sodium metavanadate in humans with insulin-dependent
and non-insulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metabol., 80:3311-20.
43. Gulla, J., and Singer, A.J. (2000). Use of alternative therapies among emergency department patients. Ann. Emerge. Med. 35: 226 -228.
44. Gupta, R., and Guptha, S. (2010). Strategies for initial management of hypertension. Indian. J. Med. Res., 132: 531-542.
45. Halat, K.M., and Dennehy, C.E. (2003). Botanicals and dietary supplements in diabetic peripheral neuropathy. J. Am. Board. Family Pract., 16: 47-57.
46. Halsad, C.H. (2003). Dietary supplements and functional foods: 2 sides of a coin. American J. Clinic. Nutri., 77:1001-1007.
47. Hartweg, J., Farmer, A.J., Perera, R., Holman, R. R , and Neil, H.A. (2007). Meta-analysis of the effects of n-3 polyunsaturated fatty acids on lipoproteins and
other emerging lipid cardiovascular risk markers in patients with type 2 diabetes. Diabetologia., 50(8):1593-1602.
48. Hartweg, J., Perera, R., Montori, V.M., Dinneen, S.F., Neil, A.H.A.W.N., and Farmer, A.J. (2008). Omega-3 polyunsaturated fattyacids (PUFA) for type 2
diabetes mellitus. Cochrane Database of Systematic Reviews; 2008. doi:10.1002/14651858.CD003205.pub2. Issue 1.Art. No.: CD003205.
49. Hodgson, J.M., Watts, G.F., Playford, D.A., Burke, V., and Croft, K.D. (2002). Coenzyme Q10 improves blood pressure and glycemic control: A controlled
trial in subjects with type 2 diabetes. Eur. J. Clinic. Nutri., 56; 1137-1142.
50. Holt, R.I.G. (2004). Diagnosis, epidemiology and pathogenesis of diabetes mellitus: an update for psychiatrists. The British Journal of Psychiatry 184: 47-55
doi: 10.1192/bjp.
51. Hooper, L., Thompson, R.L., Harrison, R.A., Summerbell, C.D., Ness, A.R., Moore, H.J., Worthington, H.V., Durrington, P.N, Higgins, J.P.T., Capps, N.E.,
Riemersma, R.A., Ebrahim, S.B.J., and Davey Smith, G. (2006). Risks and benefits of omega-3 fats for mortality, cardiovascular disease and cancer:a systematic review.
Achieves of British Med. Journal., 332:752-760.
52. Huisman, M., Kunst, A.E., Andersen, O., Bopp, M., Borgan, J.K., Borrell, C., Costa, G., Deboosere, P., Desplanques, G., Donkin, A., Gadeyne, S., Minder,
C., Regidor, E., Spadea, T., Valkonen, T., and Mackenbach, J.P. (2004). Socio-economic inequalities in mortality among the elderly in 11 European populations. J.
Epidemiol. Comm. Health., 58:468–475. International Diabetes Federation (2011).
53. Jacob, S., Henriksen, E.J., Schiemann, A.L., Simon, I., Clancy, D.E., Tritschler, H.J., Jung, W.I., Augustin, H.J., and Dietze, G.J. (1995). Enhancement of
glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittel-Forschung., 45(8): 872-874.
54. Jacob, S., Henriksen, E.J., Tritschler, H.J., Augustin, H.J., and Dietze, G.J. (1996). Improvement of insulin-stimulated glucose-disposal in type 2 diabetes
after repeated parenteral administration of thioctic acid. Exp. Clin. Endocrinol. Diabetes., 104 (3): 284-288.
55. Jellin, J.M., and Gregory, P.J. (2007). Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 9th ed. Stockton, CA: Therapeutic
Research Faculty.
56. Jiang, Q., Chrieten, S., Shigenaga, M.K., and Ames, B.N. (2001). γ- Tocopherol, the major form of Vitamin E in the US diet deserves more attention. Ame.
Soc. Clinic. Nutri., 74 (6): 714-722.
57. Johnson, M.A., Smith, M.M., and Edmonds, J.T. (1998). Copper, iron, zinc, and manganese in Dietary supplements, infant formulas, and ready-to-eat
breakfast cereals. Ame. J. Clinic. Nutri., 1035-1040.
58. Kaczmar, T. (1998). Herbal support for diabetes management. Clinical Nutrition Insights CNI608 5/98, Vol. 6, No.8.
59. Kearney, P.M., Whelton, M., Reynolds, K., Muntner, P., Whelton, P.K., and He, J. (2005). Global burden of hypertension: analysis of worldwide data.
Lancet., 365:217-223.
60. Khan, A., Safdar, M., Ali Khan, M.M., Khattak, K.N., and Anderson, R.A. 2003. Cinnamon improves glucose and lipids of people with type 2
diabetes. Diabetes Care 26:3215- 3218.
61. Kim, J.A., Formoso, G., Li, Y., Potenza, M.A., Marasciulo, F.L., Montagnani, M., and Quon, M.J. (2007). Epigallocatechin gallate, a green tea polyphenol,
mediates NO-dependent vasodilation using signaling pathways in vascular endothelium requiring reactive oxygen species and Fyn. J. Bio. Chem., 282(18):13736-13745.
Afolayan and Wintola Afr J Tradit Complement Altern Med. (2014) 11(3):248-258
http://dx.doi.org/10.4314/ajtcam.v11i3.35
257
62. Knentz, A.J., and Nattras, M. (1991). Diabetic ketoacidosis, non ketotic hyperosmolar coma and lactic Acidosis. In: Handbook of diabetes (Pickup JC and
Williams, G,eds) (2nd edition). Blackwell Science, pp.479-494.
63. Konrad, T., Vicini, P., Kusterer, K., Hoflich, A., Assadkhani, A., Bohles, H.J., Sewell, A., Tritschler, H.J., Cobelli, C., and Usadel, K.H. (1999) α-Lipoic acid
treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes. Dia Care., 22:280–
287.
64. Kotchen, T.A., and McCarron, D.A. (1998). Dietary electrolytes and blood pressure: A statement For Healthcare Professionals from the American Heart
Association Nutrition Committee. Circulation., 98:613-617.
65. Kotchen, J.M., McKean, H.E., and Kotchen, T.A. (1982). Blood pressure trends with aging. Hypertension., 4:128- 134.
66. Kumar, P.J., and Clark, M. (2002). Textbook of clinical medicine. Saunders, London, pp 1099-1121.
67. Larsson, S.C., and Wolk, A. (2007). Magnesium intake and risk of type 2 diabetes: a meta-analysis. J. Intern. Med., 262(2):208-214.
68. Litovitz, T.L., Klein-Schwartz, W., White, S., Cobaugh, D.J., Youniss, J., Omslaer, J.C., Drab A., and Benson, B.E. (2001). 2000 Annual report of the
American Association of Poison Control Centers Toxic Exposure Surveillance System. Ame J. Emergency Med., 19:337-395.
69. Mackenzie, T., Leary, L., and Brooks, W.B. (2007). The effect of an extract of green and black tea on glucose control in adults with type 2 diabetes mellitus:
double-blind randomized study. Metabol., 56(10):1340-1344.
70. Mangoni, A.A., Sherwood, R.A., Swift, C.G., and Jackson, S.H. (2002). Folic acid enhances endothelial function and reduces blood pressure in smokers: a
randomized controlled trial. J. Internal Med., 252:497-503.
71. Mansoor, G.A. (2001). Herbs and alternative therapies in the hypertension clinic. American J. Hyperten., 14: 971-975.
72. Marchioli, R., Barzi, F., Bomba, E., Chieffo, C., Di Gregorio, D., Di Mascio, R., Franzosi, M.G., Geraci, E., Levantesi, G., Maggioni, A.P., Mantini, L.,
Marfisi, R.M., Mastrogiuseppe, G., Mininni, N., Nicolosi, G.L., Santini, M., Schweiger, C., Tavazzi, L., Tognoni, G., Tucci, C., Valagussa, F., and GISSI-Prevenzione
Investigators. (2002). Early Protection against death by n-3 polyunsaturated fatty acid after myocardial infarction: time-course analysis of the results of the Gruppo
Italiano per lo studio della Sopravvienza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation, 105: 1897-1903.
73. Martin, J., Wang, Z.Q., Zhang, X.H., Wachtel, D., Volaufova, J., Mathews, D.E., and Cefalu, W.T. (2006). Chromium picolinate supplementation attenuates
body weight gain and Increases insulin sensitivity in subjects with type 2 diabetes.Dia Care., 29 (8):1826-1832.
74. McCarron, D.A. (1997). Role of adequate dietary calcium intake in the prevention and management of salt-sensitive hypertension. Am. J. Clinic Nutri.,
65:712-716.
75. McCarty, M.F. (1999). High-dose biotin, an inducer of glucokinase expression, may synergize With chromium picolinate to enable a definitive nutritional
therapy for type II diabetes. Med. Hypotheses., 52: 401-406.
76. McCormick, D. (2006). Vitamin B6. In: Bowman B, Russell R, eds. Present Knowledge in Nutrition. 9th ed. Washington, DC: International Life Sciences
Institute.
77. Merchant, R.E., and Andre, C.A. (2001). Nutritional supplement Chlorella pyrenoidosa in the treatment of fibromyalgia, hypertension and ulcerative colitis.
Alternative Therapies in Health and Medicine.,7(3): 79-91.
78. Mohamadi, A., Jarrell, S.T., Shi, S.J., Andrawis, N.S., Myers, A., Clouatre, D., and Preuss, H.G. (2000). Effects of wild versus cultivated garlic on blood
pressure and other parameters in hypertensive rats.Heart Dis., 2:3-9.
79. Moller, D. E. and Flier, J. S. (1991). “Insulin resistance-mechanisms, syndromes, and implications,” The New England J. Med., 325 (13): 938–948, 1991.
80. Morris, M.C., Evans, D.A., Bienias, J.L., Tangney, C.C., Bennett, C.C., and Aggarwal, N. (2002). Dietary intake of antioxidant nutrients and the risk of
incident Alzheimer disease in a biracial community study. J. Am. Med. Ass., 287:3230-3237.
81. Mukherjee, B., Anbazhagan, S., Roy, A., Ghosh, R., and Chatterjee, M. (1998). Novel implications of the potential role of selenium on antioxidant status in
streptozotocin induced diabetic mice. Biomed. Pharmacother., 52(2):89-95.
82. Ness, A.R., Chee, D., and Elliott, P. (1997). Vitamin C and blood pressure: an overview. J. Human Hyperten., 11:343-350. National Institutes of Health
Office of Dietary Supplements: Dietary supplement fact sheet: chromium[article online]. Available fromhttp://ods.od.nih.gov/factsheets/chromium.asp#en35. Accessed
19 February 2013.
83. Palmer, M.E., and Howland, M.A. (2001). Herbals and dietary supplements. In: Ford M et al, eds. Clinical toxicology. Philadelphia: WB Saunders: 316–31.
84. Palmer, M., and Betz, J. Plants. (2002). In: Goldfrank LR, Flomenbaum NE, Lewin NA, et al, eds. Goldfrank’s toxicologic emergencies 7th edn. New York:
McGraw-Hill: 1150–82.
85. Paolisso, G., D’Amore, A., Giugliano, D., Ceriello, A., Varricchio, M., and D’Onofrio, F. (1993). Pharmacologic doses of vitamin E improve insulin action in
healthy subjects and non-insulin dependent diabetic patients. Am. J. Clinic. Nutri., 57: 650- 656.
86. Paolisso, G., D’Amore, A., Balbi, V., Volpe, C., Galzerano, D., Giugliano, D., Sgambato, S., Varricchio, M., and D’Onofrio, F. (1994). Plasma vitamin C
affects glucose homeostasis in healthy subjects and in non-insulin dependent diabetes. Am J. Physiol., 266: 261- 268.
87. Paolisso, G., Balbi, V., Volpe, C., Varricchio, G., Gambardella, A., Saccomanno, F., Ammendola, S., Varricchio, M., and D’Onofrio, F. (1995). Metabolic
benefits deriving from chronic vitamin C supplementation in aged non-insulin dependent diabetics. J. Am. Coll. Nutr., 14:387–392.
88. Pemberton, J. (2006). "Medical experiments carried out in Sheffield on conscientious objectorsto military service during the 1939–45 war". Int. J. Epidemiol.,
35 (3): 556-558.
89. Phillips, A.W., and Osborne, J.A. (2000). Survey of alternative and nonprescription therapy use. Am. J. Health Syst. Pharm., 57:1361–1362.
90. Potenza, M.A., Marasciulo, F.L., Tarquinio, M., Tiravanti, E., Colantuono, G., Federici, A., Kim, J.A., Quon, M.J., and Montagnani, M. (2007). EGCG, a
green tea polyphenol, improves endothelial function and insulin sensitivity, reduces blood pressure, and protects against myocardial I/R injury in SHR. Am. J. Physiol.
Endocrinol. Metab., 292:1378–1387.
91. Preuss, H.G., Jarrell, S.T., Scheckenbach, R., Lieberman, S., and Anderson, R.A. (1998). Comparative Effects of Chromium, Vanadium and Gymnema
Sylvestre on Sugar Induced Blood Pressure Elevations in SHR. J. Am. College Nutri., 17 (2): 116-123.
92. Prisco, D., Paniccia, R., Bandinelli, B., Filippini, M., Francalanci, I., Giusti, B., Giuriani L., Gensini G.F., Abbate R., and Neri Serneri G.G. (1998). Effect of
medium-term supplementation with a moderate dose of n-3 polyunsaturated fattyacids on blood pressure in mild hypertensive patients. Thromb Res., 91:105–112.
93. Rang, H.P., Dale, M.M., and Ritters, J.M. (1991). The endocrine pancreas and the control of blood glucose, in pharmacology, Simmons, B. and Beasley, S.
eds, Longman Group Ltd., UK, pp 403-410.
94. Rasmussen, C.B., Glisson, J.K., and Minor, D.S. (2012). Dietary Supplements and HypertensionPot ential Benefits and Precautions - A review. The J.
Clinical. Hyperten., 14(7):467-471.
95. Reljanovic, M., Reichel, G., Rett, K., Lobisch, M., Schuette, K., Moller, W., Tritschler, H.J., and Mehnert, H. (1999).Treatment of diabetic
polyneuropathy with the antioxidantthioctic acid (alpha-lipoic acid): a two year multicenter randomized double blind placebo controlled trial. Free. Radic. Biol. Med.,
31:171-179.
96. Rother, K.I. (2007). "Diabetes Treatment- Bridging the Divide". N. Engl. J. Med., 356 (15): 1499-1501.
97. Ryu, O.H., Lee, J., Lee, K.W., Kim, H.Y., Seo, J.A., Kim, S.G., Kim, N.H., Baik, S.H., Choi, D.S., and Choi, K.M. (2006). Effects of green tea consumption
on inflammation, insulin resistance and pulse wave velocity in type 2 diabetes patients. Diabetes. Res. Clinic. Practice., 71(3):356-358.
98. Salardi, S., Cacciari, E., Sassi, S., Grossi, G., Mainetti, B., Casa, C.D., Pirazzoli, P., Cicognani, A., and Gualandi, S. (2000). Homocysteinemia, serum folate
and vitamin B12 in very young patients with diabetes mellitus type 1. J. Pediatr. Endocrinol. Metab., 13:1621-1627.
99. Schaumburg, H., Kaplan, J., Windebank, A., Vick, N., Rasmus, S., Pleasure, D., and Brown, M.J. (1983). Sensory neuropathy from pyridoxine abuse. A new
megavitamin syndrome. New Engl. J. Med., 309: 445-448.
Afolayan and Wintola Afr J Tradit Complement Altern Med. (2014) 11(3):248-258
http://dx.doi.org/10.4314/ajtcam.v11i3.35
258
100. Schulze, M.B., Schulz, M., Heidemann, C., Schienkiewitz, A., Hoffmann, K., and Boeing, H. (2007). Fiber and magnesium intake and incidence of type 2
diabetes: a prospective study and meta-analysis, Archives Intern. Med., 167 (9): 956–965.
101. Sharma, A.K. (1993). Diabetes mellitus and its complications: An update. Galadari EO, Behara I, Manchandra M, Abdulrazzaq SK, Mehra MK (eds)
Macmillian, New Delhi.
102. Sheela, C.G., and Augusti, K.T. (1992). Antidiabetic effects of S-ally cysteine sulphoxide isolated from garlic Allium sativum Linn. Ind. J. Experiment. Bio.,
30:523-526.
103. Singh, R.B., Sul, I.L., Singh, V.P., Chaithiraphan, S., Laothavorn, P., Sy, R.G., Babilonia, N.A., Rahman, A.R.A., Sheikh, S., Tomlinson, B., and Sarraf-
Zadigan, N. (2000). Hypertension and stroke in Asia: prevalence, control and strategies in developing countries for prevention. J. Human Hyperten., 14: 749-763.
104. Singh, R.B., Niaz, M.A., Rastogi, S.S., Shukla P.K., and Thakur A.S. (1999). Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance
in hypertensive patients with coronary artery disease. J. Hum. Hypertens., 13:203–208.
105. Sitasawad, S., Deshpande, M., Katdare, M., Tirth, S., and Parab, P. (2001). Beneficial effect of supplementation with copper sulfate on STZ-diabetic mice
(IDDM). Diabetes. Res. Clin. Pract., 52: 77-84.
106. Soetan, K.O., Olaiya, C.O. and Oyewole, O.E. (2010). The importance of mineral elements for humans, domestic animals and plants; A review. Afr. J. Food.
Sci., 4 (5): 200- 222.
107. Spence, J.D. (1996). Cerebral consequences ofhypertension: Where do they lead? J. Hypertens. Suppl.14: S139–S145.
108. Spencer, J. (2004). The risk of mixing drugs and herbs. Wall Street Journal June 22, 2004:D1.
109. Stapleton, S.R. (2000). Selenium: an insulin-mimetic. Cell. Mol. Life. Sci., 57:1874-1879.
110. Sunmonu, T .O., and Afolayan, A.J. (2013). Evaluation of Antidiabetic Activity and Associated Toxicity of Artemisia afra Aqueous Extract in Wistar Rats.
Evidence-Based. Complementary andAlternative Medicine. Volume 2013 Article ID 929074, 8 pages
111. Tabassum, N. and Ahmad, F. (2011). Role of natural herbs in the treatment of hypertension. Pharmacog. Rev., 5:30-40.
112. Timbo, B.B., Ross, M.P., McCarthy, P.V., and Lin, C.J. (2006). Dietary supplements in a National Survey: Prevalence of Use and Reports of Adverse Events.
J. Am. Diet. Ass., 106:1966-1974.
113. Touyz, R.M. (1991). Magnesium supplementation as an adjuvant to synthetic calcium channel antagonists in the treatment of hypertension. Med.
Hypotheses., 36: 140-141.
114. Trofimiuk, E, Braszko, J.J. (2011). Long-term administration of cod liver oil ameliorates cognitive impairment induced by chronic stress in rats. Lipids.,
46(5): 417-423.
115. Van Breemen, R.B., Fong, H.H., and Farnsworth, N.R. (2007). The role of quality assurance and standardization in the safety of botanical dietary
supplements. Chem. Res. Toxicol., 20:577-582.
116. Van Dijk, R.A., Rauwerda, J.A., Steyn, M., Twisk, J.W., and Stehouwer. C.D. (2001). Long-term homocysteine-lowering treatment with folic acid plus
pyridoxine is associated with decreased blood pressure but not with improved brachial artery endothelium-dependent vasodilation or carotid artery stiffness: a 2-year,
randomized, placebo-controlled trial. Arteriole. Thrombo. Vas. Bio., 21: 2072-2079.
117. Vasdev, S., Longerich, L., Gill, V., and Singal, P. (2002). Dietary management of hypertension. Kuwait Med. Journ., 34 (1) 2-11.
118. Warner, M.G. (2000). Complementary and alternative therapies for hypertension. Complementary Health Practice Review 6:11-19.
119. Weiss, D. (2000). Cardiovascular disease: risk factors and fundamental nutrition. International J. Integra. Med., 2: 6-12.
120. World Health Organization Department of Non-communicable Disease Surveillance (1999). Definition, Diagnosis and Classification of Diabetes Mellitus and
its Complications (PDF).
121. World Health Organization. (2002). Integrated management of cardiovascular risk. Geneva:
122. WHO, (2002). http://whqlibdoc.who.int/publications/9241562242.pdf (accessed 20 June, 2012).
123. World Health Organisation. (2003). The world health report 2003. International Society of Hypertension (ISH) statementon management of hypertension. J.
Hyper., 21: 1983-1992
124. Wild, S., Roglic, G. Green, Sicree, R., and King, H. ( 2004). “Global prevalence of diabetes: estimates for the year 2000 and projections for 2030,” Diabetes
Care, vol. 27, no. 5, pp. 1047-1053.
125. Winslow, L.C., and Kroll, D.J. (1998). Herbs as medicine. Arch. Intern. Med.,158: 2192-2199.
126. Wise, E. (2004). Twelve dangerous dietary supplements identified by ‘Consumer Reports’ widely used herbs linked to several serious ailments. USA Today,
April 8, 9D.
127. www.wikipedia.org . Dietery supplement Retrieved 14/102/2014.
128. Yosefy, C., Viskoper, J.R., Laszt, A, Priluk R., Guita E., Varon D., Illan Z., Berry E.M., Savion N., Adan, Y., Lugassy, G., Schneider R., and Raz, A. (1999).
The effects of fish oil on hypertension,plasma lipids and hemostatis in hypertensive, obese yslipidemic patients with and without diabetes mellitus. Prostaglandins
Leukot Essent Fatty Acids., 61:83-87.
129. Yusuf, S., Reddy, S., Ounpuu, S., and Anand, S. (2001). Global burden of cardiovascular diseases. Part 1: General considerations, the epidemiologic
transition risk factors and impact of urbanization. Circulation., 104: 2746-2753.
130. Ziegler, D., Hanefeld, M., Ruhnau, K.J., Meibner, H.P., Lobisch, M., Schuette, K., and Gries, F.A. (1995). Treatment of symptomatic diabetic
peripheral neuropathy with the anti-oxidant “lipoic acid”:a 3 week multicentre randomized controlled trial (ALADIN Study I). Diabetologia 38:1425-1433.
