The Susceptibility of South Asians to Cardiometabolic Disease as a Result of Starvation Adaptation Exacerbated During the Colonial Famines

Abstract

South Asians, representing one quarter of the world's population, have disproportionally high rates of obesity and cardiometabolic disease thus resulting an epidemic health crisis. This crisis could be the consequence of epigenetic effects exacerbated during the colonial-era famines resulting in a unique starvation-adapted physiology. Due to evolutionary mismatch in circumstances of abundance, this starvation-adapted physiology can become harmful. Evidence for this starvation adaptation in South Asians includes high body fat and unfavorable adipokines; low lean body mass; lower resting energy expenditure (compounded by lack of brown adipose tissue); greater insulin resistance and insulin response; exaggerated lipemic response to fat and sugar intake; less capacity to handle an overabundance of food; lower fat burning (oxidative capacity) and VO2max during aerobic exercise; and energy-conserving response to resistance exercise, as well as increased lipoprotein (a) levels. The Roma people, also of South Asian ancestry, may represent an interesting pre-colonial historical control. Physician and patient knowledge of this unique physiology in South Asians will promote a stronger physician-patient relationship and foster compliance with treatment.

Full text

Endocrinology, Diabetes and Metabolism Journal
Volume 6 Issue 2
Research Open
Endocrinol Diabetes Metab J, Volume 6(2): 1–9, 2022
Research Article
The Susceptibility of South Asians to Cardiometabolic
Disease as a Result of Starvation Adaptation
Exacerbated During the Colonial Famines
Mubin I Syed1,2,3*, Feras Deek1 and Azim Shaikh1
1Dayton Interventional Radiology, 3075 Governors Place Blvd., Ste. 120, Dayton, OH 45409, USA
2Boonshoft School of Medicine at Wright State, 3640 Colonel Glenn Hwy, Dayton, OH 45435, USA
3Springeld Regional Medical Center, 100 Medical Center Drive, Springeld, OH 45504, USA
*Corresponding author: Mubin I. Syed, Dayton Interventional Radiology, 3075 Governors Place Blvd, Ste. 120, Dayton, OH 45409, USA
Received: September 23, 2022; Accepted: September 23, 2022; Published: October 07, 2022
Abstract
South Asians, representing one quarter of the world’s population, have disproportionally high rates of obesity and cardiometabolic disease thus resulting
an epidemic health crisis. This crisis could be the consequence of epigenetic eects exacerbated during the colonial-era famines resulting in a unique
starvation-adapted physiology. Due to evolutionary mismatch in circumstances of abundance, this starvation-adapted physiology can become harmful.
Evidence for this starvation adaptation in South Asians includes high body fat and unfavorable adipokines; low lean body mass; lower resting energy
expenditure (compounded by lack of brown adipose tissue); greater insulin resistance and insulin response; exaggerated lipemic response to fat and
sugar intake; less capacity to handle an overabundance of food; lower fat burning (oxidative capacity) and VO2max during aerobic exercise; and energy-
conserving response to resistance exercise, as well as increased lipoprotein (a) levels. The Roma people, also of South Asian ancestry, may represent an
interesting pre-colonial historical control. Physician and patient knowledge of this unique physiology in South Asians will promote a stronger physician-
patient relationship and foster compliance with treatment.
Introduction
At approximately one-quarter of the world’s population, South
Asians represent one of the largest populations globally [1]. It is widely
recognized that South Asians have higher cardiometabolic risks than
people of other ethnicities. South Asians have the highest abdominal
and visceral fat (truncal obesity) per given BMI [2,3]. South Asians
are up to four to ve fold more likely to develop type II diabetes when
compared to the white populations of both the United States (US) and
United Kingdom (UK), respectively [4,5]. Additionally, South Asians
are more than twice as likely to develop metabolic syndrome than
Europids in the UK [6]. eir risk of atherosclerotic cardiovascular
disease (ASCVD) is four times greater than the general US population
[7,8]. Moreover, ethnic Asian-Indians were reported to have higher
median coronary artery calcium scores (CAC score, one of the most
important predictors for ASCVD risk) [9] than all other ethnicities
studied (i.e., Caucasian, Hispanic, African-Americans and East
Asians) [8]. is is a veritable health crisis, given the size of the South
Asian population and their higher risk of cardiometabolic disease [7].
Some of this risk could be due to lifestyle and dietary factors.
South Asians on average spend less time exercising than the general
population [10-12]. Studies have shown that the intake of rened
carbohydrates, saturated fats, fried foods, and processed foods is high
among South Asians [13-19]. However, there is a large amount of
evidence pointing to a unique physiology among South Asians that
likely has a genetic basis and represents resistance or adaptation to
starvation. ese adaptations have been suggested to predispose South
Asians to cardiometabolic disease in an environment of abundance
[20-23]. erefore, it can be argued that the susceptibility of South
Asians to cardiometabolic disease may be linked to starvation and
famine adaptation. Furthermore, it is proposed that the near 200-
year period of recurring, severe famines that occurred under British
colonial rule may have had a role in shaping the current physiology
of South Asians. e current review will shed light on the connection
between the emerging evidence correlating nutritional deprivation
and transgenerational susceptibility to cardiometabolic disease with
the culprit being the colonial famines.
e Multiple Famines and Starvation in South Asia
During the British Colonial Period
Prior to British colonial rule in South Asia, from the early
fourteenth to the end of the seventeenth centuries, major famines
occurred once every y years. ese famines were also limited in
geographical extent [24].
During colonial rule the nature and frequency of famines changed
drastically. Famines were quite prevalent in South Asia during the
British colonial period (1757 to 1947). e economic historian Mike
Davis recounts 31 major famines in the 190 years of British colonial
rule, compared to only 17 famines in the 2000 years prior [25]. Famines
accelerated in frequency as British rule consolidated and spread. is

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Mubin I Syed (2022) The Susceptibility of South Asians to Cardiometabolic Disease as a Result of Starvation Adaptation Exacerbated During the
Colonial Famines
spread is demonstrated by the occurrence of twelve serious famines
and four severe scarcities between 1765 and 1858 (roughly the rst
90 years of British rule) [24]. is is compared to acceleration in the
frequency of severe famines during the period between 1850 and 1899
(50 years during ongoing British rule) where there were 24 major
famines in South Asia [26].
e severity of the famines in South Asia made them some of the
worst in world history. ree of the ten deadliest famines and six of
the twenty-ve worst drought-associated famines that were coupled
with drought occurred in colonial India [27,28]. Additionally, the
geographically widespread nature of the South Asian famines during
colonial times was unprecedented in South Asian history. ese
famines aected areas of South Asia that were previously immune
to famine, such as Marwar and Bengal [24]. us, the famines were
more frequent, widespread, aected larger numbers of people, and
increased in intensity (as nationwide catastrophes) during British rule.
Even when famines did not occur, undernourishment was the norm
during the colonial period [29]. Food grain availability per capita, a
quantiable parameter of the degree of undernourishment, decreased
due to impoverishment from 200 kg in 1900 to 157 kg on the eve of
World War II and further declined to 137 kg by 1946 [30]. Given
South Asians continual exposure to severe famines, it makes sense to
look at how that may have had long-term eects.
How Does Famine Aect Cardiometabolic Risk in
Future Generations (Epigenetics)?
It has been shown that an adverse environment for a community
in the past can have a long-term negative health consequence in the
present [31]. Exposure of a population to just one famine is known
to increase the risk of diabetes and ASCVD via multigenerational
epigenetic eects [32]. ese eects and their duration over multiple
generations have been observed in worm and mouse models [32,33].
In humans, this epigenetic eect of famines has also been shown to
increase cardiometabolic risk. Specically, multiple studies of dierent
populations in Sweden, China, and the Netherlands have shown
this epigenetic-induced increase in cardiometabolic risk among
descendants (including the grandchildren) of famine survivors [34-
36]. One evidence of epigenetic change in Chinese famine survivors is
the high incidence of DNA methylation [21,22,37].
Based on the severity and frequency of the famines in South
Asia during the colonial period, we postulate that these famines had
a lasting epigenetic eect on the predisposition of South Asians to
cardiometabolic disease. Indeed, South Asians who develop type II
diabetes have a much higher rate of DNA methylation, an established
indicator of epigenetic change, than do Caucasians. is nding may
explain the increased incidence of type II diabetes. e relationship
of DNA methylation to type II diabetes is so strong that it has been
postulated that this biomarker may be a potential future screening tool
for early intervention prior to diabetes onset [38].
e Recent Overabundance of Food Availability in
South Asia Causes Evolutionary Mismatch
During the last 25 years, there has been a rapid increase in
prosperity, and thus, food availability, in South Asia and amongst the
South Asian diaspora [39]. is increase has led to rising incidence
rates of noncommunicable diseases (NCDs) such as heart disease,
stroke, and type II diabetes. is implies that there may be an
evolutionary mismatch of genetic traits that were once advantageous
for survival during food scarcity and have since become detrimental
in the current environment of abundance; this is also known as the
“thriy gene” or “thriy phenotype” hypothesis [40].
How do the Unique Physiological Traits of South Asian
Populations Point to Starvation Adaptation?
In support of the “thriy gene” hypothesis, studies in animal
models have revealed starvation adaptation (or starvation resistance)
aer exposure to food shortages. For example, in Drosophila, these
adaptations include sequestering greater energy reserves (greater
lipid accumulation) and reducing the rate at which energy reserves
are used (reduction in the metabolic rate and lower activity level of
the organism) [41]. Additionally, the physiological equivalence of
insulin resistance has also been demonstrated in Drosophila as a
sign of starvation adaptation [42]. ese traits of starvation adaption
appear to be transgenerational in Caenorhabditis elegans as well [33].
Further investigation is needed, but, on the basis of these animal
studies and the historical famines in South Asia, it is hypothesized that
South Asians may express some of these traits due to generations of
starvation adaptation [43].
e Unique and Dierent Physiology of South Asians
As suggested above, the physiology of South Asians is dierent
from that of other ethnicities regarding important cardiovascular and
metabolic measures. e topics discussed below outline the specic
physiological dierences seen in South Asians and relate them to
starvation/famine adaptation.
High Body Fat and Unfavorable Adipokines
It is reasonable to assume that a propensity to store body fat is
conducive to surviving famine. South Asians have a form of obesity
that is dierent from that of most populations, which is referred
to as the “thin-fat phenotype.” is characterization refers to a
disproportionate amount of body fat typically concentrated in the
abdomen in an otherwise lean individual, who oen has a normal
BMI. In fact, South Asians have the highest body-fat percentages and
lowest lean mass of any ethnicity in the USA [44,45]. Compared with
populations of European ancestry, South Asians have a total body-
fat composition that is 3-5% higher for any given BMI [46]. Notably,
South Asians have especially high levels of body fat and are more
prone to developing obesity [47,48].
Higher body-fat percentages in South Asians is characterized by
increased secondary storage in deep and visceral fat (though supercial
subcutaneous fat is reduced); ectopic fat (such as intramyocellular
and intrahepatic fat deposition); adipocyte hypertrophy; and a less
favorable adipokine prole, which are cytokines produced in fat cells
that regulate metabolism, energy, and inammation; this condition
is referred to by some as “ethnic lipodystrophy” [44,49-52]. Of note,
South Asians have been shown to have the tendency to store ectopic
fat as hepatic fat compared with other ethnicities, which is associated

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Mubin I Syed (2022) The Susceptibility of South Asians to Cardiometabolic Disease as a Result of Starvation Adaptation Exacerbated During the
Colonial Famines
with greater hepatic insulin resistance [53]. Regarding the adipokine
prole, the levels of adiponectin, which promotes peripheral insulin
sensitivity, are lower in South Asians, and the levels of resistin, another
adipokine that promotes insulin resistance and obesity, are higher in
South Asians [44,54,55].
Low Lean Body Mass
In addition to having higher body fat percentages, South Asians
have lower lean body mass levels than do people of other ethnicities. It
is hypothesized that part of the reason for this is that South Asians have
higher expression of the gene encoding myostatin [50,56]. Myostatin
is a protein found in skeletal muscle that inhibits its growth. is
hypothesized eect would explain why a higher body fat percentage
and low lean mass exists among newborns of South Asian migrants to
the UK, Netherlands, and Surinam that persists for at least four to ve
generations [57,58]. Low lean body mass is associated with higher rates
of insulin resistance and cardiovascular disease (CVD) risk [59-61].
Numerous severe famines aected South Asia throughout the 19th
and rst half of the 20th centuries. e eects were worsened by British
colonial policy, which led to a high mortality rate from the starvation
that occurred [57]. Lean mass (especially, muscles and organs) is
known to consume calories at a higher rate than fat. erefore, the
intense selection pressure from the numerous severe famines of the
19th and rst half of the 20th centuries would have favored low levels
of lean mass in addition to a higher body fat percentage.
e low lean mass of South Asians has been postulated to be
one of the evolutionary reasons for the higher incidence rates of
NCDs, such as cardiometabolic disease, in this population. Previous
research has implicated colonial famines as a major exacerbator of
the development of low lean mass due to starvation adaptation [58].
One study suggested that South Asians have had historically low
lean mass for at least 11,000 years due to a variety of factors (such
as delayed transitions from foraging to agriculture and the change to
a predominantly vegetarian diet) [57]. However, we believe that the
epigenetic eects of the famines on the South Asian physiology during
the colonial period cannot be discounted.
ree factors that support the severity of the eects of these
colonial famines are the exceedingly high death toll (up to 85 million
deaths); the documented decrease in life expectancy during this
period; and the decrease in stature (height) compared to an increase
in stature in most of the other populations worldwide) [25,58,62-66].
Lower Resting Energy Expenditure
ermoneutral resting energy expenditure is the energy
expended necessary for basic physiological functioning at rest while
awake, fasting, and without needing to use energy to regulate body
temperature. As a result of their lower lean mass and higher body fat
at the same height, weight, and BMI compared with people of other
ethnicities, South Asians have lower thermoneutral resting energy
expenditure (burning less energy at rest, approximately 32% less
than Caucasians) [67-69]. is is another adaptation that may have
helped some South Asians survive famines. One study showed that
at the cellular level, South Asians seem to have higher mitochondrial
eciency, evidenced by the higher oxidative phosphorylation capacity
in this group compared with Americans of North European origin
[70]. e excess ATP-produced and higher oxidative state has been
shown to prevent insulin receptor deactivation, resulting in insulin
resistance [71,72].
One other reason contributing to the relative lower energy
expenditure at rest, besides higher percentages of body fat, amongst
South Asians is the lower amount of brown adipose tissue (BAT, or
brown fat) [69,73]. BAT is a type of adipose tissue that is specialized
for heat generation and can be responsible for up to 20% of total
energy expenditure in its activated mode [74]. In South Asians,
BAT volumes have been shown to be approximately 34% less than
Caucasians [69]. BAT is responsible for nonshivering thermogenesis
(heat generation). For South Asians this means a reduced capacity
to generate nonshivering thermogenesis or waste heat [69]. In
cold-adapted populations, higher levels of BAT are protective for
cardiometabolic health (including diabetes), as BAT produces
uncoupled mitochondrial respiration for heat generation that burns
o excess calories (nonshivering thermogenesis) [73]. e protective
mechanism likely involves the use of BAT burn or its metabolism of
excess calories in states of caloric overabundance [73,75].
ese phenomena may explain why amongst diaspora populations
of East Asians (who, like Caucasians, are a cold-adapted population
with relatively elevated levels of thermogenic capacity) have a much
lower predisposition to cardiometabolic disease than South Asian
diaspora populations [73]. In fact, among individuals aged 20-29 years
living in the US, the incidence of diabetes in South Asians is threefold
higher than in Chinese, as well as two times higher when compared
with individuals of European origin [53]. is nding occurs despite a
similar famine laden history in both South Asia and China [53,76,77].
In summary, regarding energy expenditure, South Asians were
substantially impacted by starvation adaptation. ese adaptations
would have promoted hyperecient mitochondria and a lack of
BAT. Both adaptations would have been helpful in promoting energy
eciency. Having less brown fat is thought to be a tropical adaptation,
although an additional benet may have been less energy consumption
during starvation [73]. However, in times of abundance, this lack of
BAT predisposes South Asians to cardiometabolic disease.
Greater Insulin Resistance/Insulin Response
Certain genetic factors involved in cardiometabolic processes
including prediabetes/diabetes have also been found to be
contributing factors to the unique South Asian physiology [43]. A
single-nucleotide polymorphism (SNP) of the MC4R gene associated
with higher levels of visceral (including hepatic) fat and insulin
resistance is highly prevalent in South Asians [78]. Furthermore,
at least six genetic variants associated with the premature onset of
insulin-resistant diabetes have been found to be much more prevalent
in South Asians than in Europeans [79]. Another study suggested that
based on genetic data (polygenic risk score), South Asians had about a
four times higher risk of type 2 diabetes than the European population
[80]. South Asians have a higher postprandial insulin response, with a
higher tendency toward insulin resistance in the overfed state (Figures

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Mubin I Syed (2022) The Susceptibility of South Asians to Cardiometabolic Disease as a Result of Starvation Adaptation Exacerbated During the
Colonial Famines
1 and 2) and there is a three- to four-fold higher prevalence of insulin
resistance in lean South Asian men than in lean men of other ethnic
groups [81,82].
Regarding fat intake, one study showed that ve days of consuming
a high-fat and high-calorie diet resulted in the development of insulin
resistance, manifesting as a reduced nonoxidative insulin-stimulated
glucose disposal rate, in all South Asian participants (but in none of
the Caucasian participants) [83]. erefore, high fat intake produces
insulin resistance more readily in South Asians. A physiological
mechanism underpinning this was recently determined to be related
to lipid droplet dynamics linked to perilipin-5 (PLIN5), a protein
that interacts with intramyocellular lipids to transport them to
mitochondria. High PLIN5 levels typically maintain insulin sensitivity
in Caucasians in response to high fat intake.
South Asians have even higher levels of PLIN5 in response to
high fat intake, yet despite these higher levels, toxic fat breakdown
products accumulate in the muscle, resulting in insulin resistance.
Lipid droplet dynamics (which involve the release of fatty acids to fuel
mitochondrial oxidation) in South Asians are therefore likely impaired
or compromised [84]. Even early in life insulin resistance is more
prominent in South Asians as the umbilical cord blood of newborns
of South Asian ancestry manifest elevated insulin levels [85,86].
It is known that insulin resistance predisposes and correlates to
cardiometabolic risk. Insulin resistance can be ameliorated by exercise.
However, in the setting of higher insulin resistance, a greater duration
of exercise may be needed to improve insulin sensitivity [87,88]. is
occurrence could explain why South Asians may need more exercise.
It is known that South Asians may need up to 80% more exercise to
stave o cardiometabolic disease. Specically, to maintain the same
level of cardiometabolic health as Caucasians, South Asians need to
exercise much more than their Caucasian counterparts. For instance,
150 minutes of moderate intensity exercise per week is recommended
for Caucasians, but the time needed for South Asians to achieve the
equivalent cardiometabolic benets of moderate intensity exercise is
232–266 minutes per week [89,90].
Insulin resistance is believed to be benecial in the starvation-
adapted individual by reducing glucose uptake by muscles [91].
More importantly, glucose would be diverted to the brain, which
does not need insulin for glucose uptake; this is known as the selsh
brain hypothesis [92-94]. Alternatively, it has been suggested that
the benets provided by insulin resistance during starvation may
actually be by preventing the net degradation of proteins [95]. Insulin
resistance also promotes lipogenesis and fat retention, both of which
would be helpful in a starvation state; this would explain why South
Asians develop insulin resistance at much lesser levels of body fat and
why the lower BMI/waist circumference (WC) cutos were established
(see below).
Exaggerated Lipemic Response to Excess Sugar and Fat
Intake (Predisposes to Insulin Resistance as a Starvation
Survival Mechanism)
Due to an elevated predisposition to insulin resistance, South
Asians have demonstrated dierent physiological responses to
Figure 1: Plasma insulin (A), glucose (B) and nonesteried fatty acid (NEFA) (C)
responses to a 75 g oral glucose load.82 Note the higher insulin response, but the equivalent
serum glucose and NEFA responses, to the same glucose load in South Asians (than that
in Europeans). us, thriiness with glucose as seen in South Asians would be a useful
starvation adaptation. [Reproduced from Hall, et al. (2010) with permission from PLOS].
Figure 2: Comparison of European men to South Asian men shows that South Asian
men have a lower insulin sensitivity index (reecting a higher insulin response to an oral
glucose load). e horizontal bars denote mean values. e P values shown are for the
dierence between the European and South Asian groups, either unadjusted or adjusted
for age, BMI and fat mass.82 is nding suggests higher insulin resistance overall in
South Asian men. Higher insulin resistance may be a useful starvation adaptation by
preserving glucose. [Reproduced from Hall, et al. (2010) with permission from PLOS].

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Colonial Famines
sugar and fat intake. Dietary sugar intake, like fructose and glucose,
in healthy South Asians with normal indices of insulin sensitivity
generates a much higher lipemic response when compared with
Caucasians, due to an enhanced hepatic de novo lipogenesis (DNL).
ere is a known negative correlation between de novo lipogenesis and
insulin sensitivity [96]. Additionally, when given a high-fat diet, South
Asians had greater adverse eects on their lipid prole and insulin
sensitivity than Europeans/Caucasians [97]. Such an exaggerated
lipemic response would be benecial as a starvation adaptation to
promote fat storage.
Less Capacity to Handle Overabundance of Food
Despite the higher tendency toward insulin resistance and high
insulin levels, South Asians have a lower beta cell reserve for insulin
secretion compared to people of any other ethnicity [50]. is
phenomenon may have been a response to the repeated famines South
Asians endured [53]. Physiological changes associated with insulin
resistance and metabolic syndrome (dysglycemia and dyslipidemia)
occur at much lower body fat levels in South Asians than they do in
people of other ethnicities [98]. ese data support the establishment of
lower BMI/ WC cutos for obesity by the World Health Organization
(WHO) and International Diabetes Federation (IDF) for the South
Asian population [99].
Possible explanations for this inability to handle a surplus of
energy is called the adipose tissue overow hypothesis [100]. e
primary compartment in which fat is stored is in the supercial
subcutaneous adipose tissue, where excess fat is inert metabolically.
As a consequence of enduring severe famine, there would be no
physiological need for a fully developed store of excess fats in the
supercial subcutaneous adipose tissue. Due to the smaller capacity of
subcutaneous fat storage available to South Asians, this compartment
is overlled much earlier than it is in Caucasians. erefore, fat
storage resumes in more metabolically active compartments (deep
subcutaneous and visceral adipose tissues), resulting in metabolic
complications such as dysglycemia and dyslipidemia at smaller BMIs
than other ethnic groups, such as Caucasians.
Such a starvation-adapted body would also need a lower beta
cell reserve for insulin secretion, possibly due to hypostimulation of
these beta cells [101,102]. Less insulin is necessary to function in a
starvation/undernourished state; however, this reduced beta cell
reserve would be more easily exhausted during a state of chronic
overnutrition (i.e., chronic insulin resistance) [103]. Interestingly,
Chinese individuals have the second lowest level of pancreatic beta
cell reserve aer South Asians [50]. is nding could also be a vestige
of adaptation to survival during numerous famines in China.
Lower Fat Burning (Oxidative Capacity) and VO2max
during Aerobic Exercise
South Asians have a lower fatty acid oxidation capability in states
of aerobic exercise, with a trend towards lower fatty oxidation in the
sedentary state [82,97,104]. Normally in the exercise state, fatty acids
are released through lipid droplet lipolysis to fuel mitochondrial
fatty acid oxidation demands [84]. Related to this, it has been found
that the fat oxidative capacity during aerobic exercise is up to 40%
lower in South Asians than in Caucasians [82]. In that study, tness
and VO2max were much lower in South Asians than in Caucasians
even though mitochondrial content and function were similar or
higher in South Asians than in Caucasians [82]. In other words, the
intramuscular expression of oxidative and lipid metabolism genes in
South Asians is not reduced, but there is still a lower oxidative capacity
in the muscle during aerobic exercise. is nding is thought to be
another manifestation of insulin resistance in South Asians that may
originate as a result of impaired lipid droplet dynamics [84]. Starvation
adaptation can explain why the South Asian phenotype favors a lower
capability to burn fat during exercise, as well as in sedentary and
overfed states.
Starvation adaptation would also explain the accumulation
of intramyocellular fat due to the mitochondrial oxidation issues
described above. is accumulation allows the oxidation of fat at a lower
rate, thereby conserving fat stores. Additionally, intramyocellular fat
accumulation impairs insulin receptors, leading to insulin resistance,
which in turn prevents the utilization of glucose by muscles [91]. A
starvation-adapted body would also be more likely to become insulin
resistant more readily from the intake of saturated fat to maximize
the storage of calories (in the form of fat, rather than burning it in
muscle).
Energy-Conserving Response to Resistance Exercise
Besides dierences in fatty acid oxidation during aerobic exercise,
there is also a dierence in response to resistance exercise among
South Asians. e physiological response to identical resistance
exercise training is less favorable among South Asians than among
Caucasians. Although muscle protein synthesis was equivalent, South
Asians had a poorer response with regard to body fat reduction, resting
carbohydrate level reduction, fat metabolism increase, VO2max
increase, and upper body strength increase [104].
Regarding systolic blood pressure reduction, South Asians also
had a worse response to exercise. It was hypothesized this was due
to reduced bioavailability (seen in prior studies with South Asians)
of nitric oxide (NO2 a potent vasodilator) in resistance endothelial
vessels that supply muscle [104-106]. It would be expected there
would be a less favorable muscle response to resistance exercise (in
regard to VO2max, less upper body muscle strength, and less fat
reduction) [104]. Instead, in the starvation-adapted individual, this
muscle response would aim to conserve calories and would be blunted.
Additionally, in the starvation state, there would be a decrease in
blood pressure reduction in response to exercise because of reduced
NO2 bioavailability [104]. A decrease in the level of NO2, which has a
vasodilatory eect in muscle, would be benecial for reducing blood
ow to the muscle and the subsequent calorie expenditure by muscle
to preserve calories for use by the brain (selsh brain hypothesis).
is may have taken place in South Asians to conserve energy in a
starvation adapted state.
Higher Lipoprotein(a) in South Asians
Vitamin C scarcity during times of famine may have led to an
adaptation that predisposes South Asians to cardiovascular disease
during times of prosperity. During famine in some areas of colonial

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Colonial Famines
India the estimated prevalence of scurvy (or acute vitamin-C
deciency) by a British colonial medical ocial was as high as 60-
70% [107]. To compensate for this, lipoprotein(a) or Lp(a), may have
become elevated in South Asians. is is because Lp(a) is a vitamin
C analog that is hypothesized to be protective against vitamin C
deciency [108]. Moreover, Lp(a) as a surrogate of vitamin C helps
in wound healing and protects against the eects of scurvy, which
is characterized by capillary fragility, hemorrhage, and inadequate
wound healing [108]. Here is how Lp(a) and cardiovascular disease
are connected. Subclinical vitamin C-deciency can occur in
modern society. is deciency can weaken arterial walls since
vitamin C is critical to maintaining the collagen framework [109].
Lp(a), in functioning as a replacement for vitamin C, tends to also
bring LDL-cholesterol to weakened arterial walls and incite plaque
development [109]. A study in mice that could not produce vitamin C
for themselves, and were enabled to produce Lp(a), showed that mice
(lower order mammals that do not usually develop atherosclerotic
plaques) developed atherosclerotic plaque when exposed to Lp(a) just
like humans [110].
It would follow that starvation-adapted populations, such as
South Asians, would have a high prevalence of elevated Lp(a) levels.
In fact, South Asians have one of the highest prevalence (40-45%)
of abnormal Lp(a) levels [111]. Lp(a) promoted survival during
famine and undernourishment when life expectancy was low such
as occurred in colonial India when it was as low as 20 years between
1910-1920 [62,63,66]. Lp(a) becomes problematic during times of
prosperity and higher life expectancy as an elevated Lp(a) level is one
of the strongest independent risk factor for premature cardiovascular
disease [110,112].
A Pre-Colonial South Asian Historical Control
Population
e Roma people (historically referred to as “gypsies”) in Europe
emigrated from northern South Asia during the eleventh century.
It is interesting to note that the Roma peoples’ rates of diabetes are
similar to or signicantly higher than rates of diabetes among white
Caucasians [113-117]. However, reports of increased prevalence
of diabetes among Roma populations are thought to occur due to
predisposing factors of lower socioeconomic status, and increased
smoking rates of the Roma people compared with the general
population who on average have higher socioeconomic status [117-
119]. is increase contrasts sharply with the four to ve times higher
rate of diabetes in South Asians living in Western countries compared
with white populations [4,5].
Additional evidence has found that the Roma people have no
increased genetic susceptibility to diabetes compared with the
general population [119]. is nding contrasts with the South Asian
populations, which has a known genetic predisposition to diabetes
[80].
e Roma may represent a historical control on the rate of diabetes
in people of South Asian ancestry without the eect of the colonial
famines. is control could potentially show how the colonial famines
may have adversely impacted the South Asian rates of diabetes.
Conclusion
Taken together, the data indicate that South Asians have a
unique physiology that may have evolved via epigenetic eects to
ensure survival during severe and frequent famines. It is likely that
these adaptations have predisposed the South Asian population to
cardiometabolic diseases in an environment of abundance.
We suggest this perspective of the unique South Asian physiology
based on a history of famines will help explain why this population is in
a veritable health crisis of cardiometabolic disease and engender future
studies. is research could be done using similar methodologies as
those used in studies on the multigenerational eects of the Great
Chinese Famine or the Överkalix Famine [34,35].
Physicians who are knowledgeable of this physiology will be
appropriately more aggressive in diagnosing and treating South
Asian patients in an ethnically sensitive fashion [120]. Physicians will
also have higher empathy for and credibility with their South Asian
patients that may ultimately lead to a higher compliance via a stronger
physician-patient relationship [121]. South Asian patients who have
a greater insight into their own bodies and history may be able to
improve their vigilance and motivation to adhere to suggested lifestyle
and medical therapies [122].
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Citation:
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