Palmitic acid and palm oil, r
eview of the literature and implications on human health
Palm oil and the fatty acid it contains most , palmitic acid, have been the subject of many studies by the scientific community in recent years, both epidemiological and laboratory studies in in-vitro and in-vivo models, regarding their effect on human health.
The media also reported on this topic in various newspapers in a more or less amplified and sometimes sensationalistic way. This brief review of the scientific literature of recent years is intended to offer an objective view of the topic.
Palmitic acid (16:0, PA) is the saturated fatty acid most commonly found in the human body. It can befood-derived or be synthesized endogenously by our cells ( de-novo synthesis). In phospholipids, important constituent molecules of cell membranes, and triacylglycerols (TGs) of adipose tissue, PA accounts for 20-30% of total fatty acids (FA)(Carta et al., 2017).
In foods, PA is found in meat and dairy products (50-60% of total fat) and in cocoa butter (26%) and olive oil (8-20%), and as the name suggests, PA is an important component of palm oil (44% of total fat). In addition, in breast milk, PA is 20-30% total fat (Innis et a., 1997). The summary de-novo of FAs in cells is by the fatty acid synthase enzyme complex, the end product of which is precisely PA having 16 carbon atoms and no double bonds (16:0).
Physiologically, PA accumulation is counteracted because normally a portion is either modified into palmitoleic acid by inserting a double bond (16:1) or elongated by forming stearic acid (18:0) and further insaturated, forming oleic acid (OA, 18:1) (Strable and Ntambi, 2010; Silbernagel et al., 2012).
Disruption of the balance of PA and its derivatives is often related to uncontrolled endogenous biosynthesis, regardless of dietary intake, which can lead to various pathophysiological conditions. In fact, it has been seen that in pathological conditions such as in obesity, insulin resistance, and nonalcoholic hepatic steatosis, there is an increase in de-novo synthesis that contributes heavily to fat deposition in the liver and changes in the fatty acid composition of phospholipids and TGs (Marques-Lopes et al., 2001).
This suggests that the desaturation of synthesized FAs. de-novo Is required to modulate TG biosynthesis and prevent lipotoxic effects due to ‘excessive accumulation of saturated fat (Collins et al., 2010) resulting in cellular dysfunction that can lead to a morbid condition, metabolic syndrome (Brookheart et al., 2009; Cnop et al., 2012). Therefore, the overproduction of synthetic PA. de-novo, activated by pathophysiological conditions and chronic nutritional imbalance, leads to a systemic inflammatory response and metabolic dysregulation, resulting in dyslipidemia, insulin resistance, and fat deposition and distribution (Donnelly et al., 2005). In the liver, for example, excess FA leads to an increase in exported TG, via VLDL lipoproteins, into the plasma. Therefore, it can be assumed that a control exists to maintain PA homeostasis, and if there is an imbalance between saturated FAs and unsaturated FAs (FAs/FAi), this may induce transient hypertriglyceridemia and hypercholesterolemia and a moderate increase in TG deposition in the liver. At the phospholipid level of cell membranes, the maintenance of FAs/FAi balance is crucial for preserving the chemical and physical properties of the membrane and thus cell function (Abbott et al., 2012).
In several tissues, the composition of cell membranes in FAs remains fairly constant even with widely varied diets, suggesting that the concentration of FAs, is regulated little by their dietary intake (Abbott et al., 2012). Most studies conducted on fasting subjects show that the contribution of liver synthesis de-novo to the total FAs pool, is modest in healthy subjects with a balanced diet. In contrast, the content of polyunsaturated fatty acids (PUFAs) ω-6 in membranes correlates with dietary introduced PUFA ω-6, and this is more true for PUFA ω-3.
Instead, the plasma content of free fatty acids (NEFA) released from adipose tissue reflects fat intake. In fact, OA and PA the most prevalent dietary FAs in plasma are about 31% and 27%.
In a recent paper, Yuan et al, (2017) showed that PA alters a cellular pathway that inhibits endothelial angiogenesis, and thus the authors suggest that excess PA might have implications in wound healing and diabetes, where altered circulatory system function is a frequent complication.
The association of circulating PA levels with cancer development is quite controversial. The association between blood fraction PA levels in relation to breast cancer risk was reported in a meta-analysis (Saadatian-Elahi et al., 2004) and a prospective study. (Bassett et al., 2016), while another prospective study conducted in northern Italy found no association between saturated fatty acids and breast cancer risk (Pala et al., 2001).
It must be remembered that PA is an essential fatty acid in that: (a) Is an essential constituent of biological membranes; (b) is the main component of lung surfactant, which is an essential substance for respiration. It is produced in the lungs by epithelial cells to reduce surface tension at the air/liquid interface of the lung alveoli; (c) is the precursor of a particular endocannabinoid, PEA, a lipid mediator with neuroprotective, anti-neuroinflammatory and analgesic properties.
Palm oil
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In recent decades, much has been debated on the possibility that a dietary intake of palm oil characterized by a high content of FAs, may to increase the likelihood of going into cardiovascular disease (CVD).
Palm oil is relatively rich in saturated fatty acids FAs, which account for about half of the total fat. Monounsaturated fatty acids (MUFAs) and PUFAs account for about 40 percent and 10 percent, respectively. In addition to its fatty acid content, palm oil native Contains several phytocompounds such as tocotrienols and tocopherols (vitamin E) that are beneficial to human health, mainly due to their antioxidant activity (Loganathan et al., 2017). Red palm oil also contains α and β-carotene and Dong et al, (2017) in a meta-analysis conclude that this oil is effective in preventing Vit A avitamosis, indicating ≤8 g/day as the optimal dose because higher doses do not lead to further increases in serum retinol concentrations.
Below is the formula for TG found in palm oil, where at the sn-1 and sn-3 position of the glycerol is esterified PA while at the sn-2 position instead is OA. When palm oil is taken up, in the gut, pancreatic lipase cuts the bonds in sn-1 and sn-3, but not in sn-2 where oleic acid remains bound and the monoglyceride is absorbed by cells. In the cell, enzymatic systems reconstruct TG by inserting into sn-1 and sn-3 preferentially saturated fatty acids such as palmitic and stearic; finally, TG will come to form together with dietary cholesterol and some apoproteins, chylomicrons, a class of lipoproteins that will then be released into the circulatory system.
By Mancini et al, 2105 Molecules 2015, 20, 17339-17361; doi:10.3390/molecules200917339
Studies comparing the effects on lipoproteins following intake of palm oil or soybean oil (a vegetable oil with more PUFAs and fewer FAs than palm oil), showed no substantial difference in serum lipid profile, except for an increase in cholesterol HDL with palm oil (Zhang et al. 1997; Muller et al. 1998; Al-Shahib and Marshall 2003; Pedersen et al. 2005; Vega-Lopez et al. 2006; Utarwuthipong et al., 2009). Comparison with olive oil showed, in some studies, either no effect or an increase in total and LDL cholesterol with palm oil (Ng et al. 1992; Choudhury et al. 1995; Truswell 2000).
A PA-enriched diet slightly increases LDL and HDL cholesterol levels but the HDL/LDL ratio, which is a valuable cardiovascular disease risk taker, changes little.
Currently there are no clear demonstrations on the negative role of PA for health and much less for native palm oil, which is a complex food matrix in which PA only one of its components.
Native palm oil, however, goes through several processes during the industrial production process. Oils, especially vegetable oils, are refined at high temperatures (about 200 °C) where they undergo partial hydrolysis of TGs with oxidation of glycerol, leading to the formation of 3-monochloropropanediol (3-MCPD) and 2-monochloropropanediol (2-MCPD). The highest levels of these compounds were observed during palm oil refining. In 2012, Codex Alimentarius recommended the use of technological adaptations to reduce 3-MCPD levels in the finished product, and in 2013, the International Agency for Research on Cancer (IARC) declared 3-MCPD as a possible human carcinogen (Group 2B). EFSA in 2017 recently updated the tolerable daily intake of 3-MCPD of 2.0 μg/kg body weight (EFSA 2018).
During industrial processing, native palm oil, like other vegetable oils, also undergoes another chemical modification, which is inter-esterification or fatty acid randomization that involves positional redistribution of FA chains within the TG leading to the formation of new molecular species. This process is intended to change the initial chemical and physical properties, making these oils more suitable for various applications in the food industry.
However, inter-esterification has also been seen to have potential adverse health effects due to the introduction at the sn-2 position of saturated fatty acid chains such as palmitic and stearic, which remain bound to glycerol, forming the monoglyceride that is absorbed by intestinal cells. It would be precisely the absorption of palmitic acid in the monoglyceride related to the increased atherogenicity of palm oil (Kritchevsky 2000).
Hayes and Pronczuk (2010) in a meta-analysis analyzed studies that correlated the risk of cardiovascular disease, with the intake of oils processed by inter-esterification. Some studies taken into examination showed that a high intake of palmitic or stearic, esterified in
sn-2,
had negative biological effects on lipoproteins, blood sugar, insulin, immune function, and liver enzymes.
Finally, a review of the literature (Hooper et al., 2012) which reviewed studies on modification on dietary fat type and cardiovascular prevention concluded that reducing and modifying dietary FAs can reduce cardiovascular risk by maintaining the same total fat consumption but replacing some of it with FAi, especially PUFAs, but not with carbohydrates. The PREDIMED study, a randomized clinical trial on in a high-risk Mediterranean population, came to the same conclusion. Zock et al, (2016), conclude that diets high in refined carbohydrates and sugars but low in fat are not effective in reducing CVD. Limiting animal fats high in FAs and replacing them with vegetable oils high in MUFAs and/or PUFAs found in fatty fish has multiple metabolic benefits and is associated with lower risks of fatal CVD and stroke. Currently, only trans fatty acids have been shown to be associated with an increased risk of CVD.
This protective effect of FAi is due to the fact that PA and OA contribute differently in insulin resistance. Studies of subjects who reduced their FAs intake while increasing their MUFA intake showed significant improvement in insulin sensitivity(Vessby et al., 2001) . Three main mechanisms have been reported in PA-mediated insulin resistance: (i) increased synthesis of deleterious complex lipids; (ii) impairment of the function of cell organelles; and (iii) inflammation mediated by receptors. In adipocytes of non-obese people, PA, increases the expression of tumor necrosis factor (TNF-α), pro-inflammatory cytokines and IL-6 and decreases mRNA levels of the anti-inflammatory cytokine IL-10 and adiponectin. In contrast, OA decreases the expression of pro-inflammatory cytokines and causes increased expression of IL-10 and adiponectin.
OA has an anti-inflammatory action, has the ability to inhibit endoplasmic reticulum stress, prevents attenuation of the insulin signaling pathway, and improves the survival of pancreatic beta cells, which produce it. In conclusion, the cellular/metabolic effect of PA and OA are the opposite of each other.
Finally, in a recent meta-analysis, Ismail et al.,(2018) that in light of current data it is difficult to establish clear evidence for or against palm oil consumption relative to CVD risk and cardiovascular disease-specific mortality. Further studies are needed to establish the association of palm oil with CVD.
However, palm oil has possible health effects if abused, depending on the high FAs concentration; its consumption, is not correlated with risk factors for cardiovascular disease in young people with normal weight and cholesterol, if its intake is counted within 10% saturated fatty acids that nutritional advice indicates as the maximum daily value for this fatty acid category. In contrast, the elderly and individuals with dyslipidemia or previous cardiovascular events or hypertension are at higher risk (Di Genova et al., 2018).
Palm oil and children
It must be remembered that monoglyceride with the PA in sn-2 (also called beta-palmitate), is a natural component of breast milk. When added to formulas it plays favorable metabolic and functional roles, with immunomodulatory and anti-inflammatory effects. In infant formula, the percentage of PA in sn-2 can be increased by using mixtures of inter-esterified triglycerides from different vegetable oils (Delplanque et al., 2015). The position of PA in sn-2 Makes it easier to absorb which promotes rapid growth in the first few months of life (Listenberger, et al.,2003; Ertunc and Hotamisligil, 2016). In human milk, optimal percentages of essential fatty acids (α-linolenic and linoleic) are also present, prevailing over saturated fatty acids, but most importantly, the stereospecific distribution of the different fatty acids in triglycerides ensures advantageous absorption.
Important point not to forget that with weaning the caloric contribution of lipids decreases from 50 to 35-40% at 3 years of age andwith a maximum of 10% in sFA, due to the concomitant increase in the amount of carbohydrates. The percentage of fat in the diet will be further decreased to 30 percent, in adulthood.
Conclusions
After an evaluation of the recent literature, the following can be stated.
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To date, there is no evidence that palm oil is a risk to human health (Marangoni et al., 2017) . The important thing is to consume it in moderation, counting it along with animal fats in the 10 percent of saturated fatty acids that nutritional advice indicates as the maximum daily value (LARN, 2014).
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It is true that native palm oil alone is a source of phytocompounds such as tocotrienols and tocopherols (vitamin E) and vitamin A.
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It is true that processed palm oil may contain toxic substances such as 2-MCPD and 3-MCPD, but in recent years the processing processes used have significantly lowered the likelihood of formation. EFSA based on scientific research has revised the maximum daily limit of 3-MCPD alone to 2.0 μg/kg body weight.
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It is true that the process of inter-esterification, which leads to increased esterification in sn-2 of PA, may have adverse biological effects on lipoproteins, blood glucose, insulin, immune function, and liver enzymes.
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It is incorrect to say that palm oil is not suitable for children. Palmitic acid is essential in childhood.
Paola Palestini
Professor of Biochemistry, Milan-Bicocca University
Coordinator of the master’s level II Food and Applied Dietetics masterADA.
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