Cottonseed Oil Problems - Cottonseed Oil is a Drug

A Little History

In 1906, an American journalist wrote a novel to portray and expose the corruption in meat packing factories exploiting immigrants with harsh working conditions in the United States. His horrifying accounts of workers falling into processing tanks and being ground along with animal parts into lard; however, shocked the public far more for food safety concerns rather than the mistreatment of workers. In response to the public's misunderstanding of the point of his book, he exclaimed, "I aimed at the public's heart, and by accident I hit it in the stomach!" As consumers bought significantly less meat, animal lard became expensive and less available for manufacturing other products such as candles and soaps.

One manufacturing company found a new and cheaper supply of a lard-like substance. Cotton plants, don’t make readily edible foods for animals or humans, but make cotton bolls around their seeds to increase the spreading of seeds using wind dispersal. Cottonseeds were an abundant and common unwanted leftover of making fabric from cotton plants. For instance, cotton gins of the time had simply left the seeds to rot or occasionally dumped them illegally into rivers. The cottonseeds’ oil could be extracted and partially hydrolyzed (turned from oil to a semi-solid) to closely resemble animal lard. Not only did the lard-like substance provide a cheaper solution to manufacturing candles and soaps, but it created an entirely new food product for humans never before available. The company effectively turned garbage into profitable household supplies and food for humans.

This new food product was welcomed into American kitchens as a pure substitute for the untrusted and possibly unsanitary animal/human lard mixture. The lard-like substance was produced in gleaming and sterile factories. Shiny tin cans over-wrapped with white paper emphasized its pristine state. Everything about the product communicated uncorrupted perfection. The perceived purity of the plant-derived, lard-like substance and its timing seemed miraculous. In the first year, over 2.5 million pounds were sold and the number reached sixty million within 5 years. Its name would become a household term for the next hundred years.

The American journalist and novelist: Upton Sinclair.[1, 2] The novel: The Jungle.[3] The company: Proctor & Gamble.[4, 5] The lard-like substance: Crisco (named for crystallized cottonseed oil).[6, 7]

Effects on Reproduction

“During the 1930s to 1940s, not a single childbirth was reported during a period of 10 yr in one area of China. Later, it was determined that for economic reasons villagers had switched from cooking with soybean oil to crude cottonseed oil.[8] In the 1960s, in many rural areas of China, villagers exhibited fatigue and felt burning sensations on body extremities. They referred to the disease as ‘burning fever.’ It was shown that these villagers likewise had been using homemade, crude cottonseed oil for cooking.[9] Several years later, many afflicted couples experienced fertility problems. Women suffered from amenorrhea and men were impotent. These epidemiological findings led to clinical studies and further animal investigations.”[10]

“Gossypol is a natural toxin in the cotton plant that protects it from insect damage, and it is also toxic to humans; in addition, it gives the crude oil its strong brownish-red color.”[11]

Gossypol acetic acid (GAA).

“In human (n = 4,000) clinical trials conducted in China, GAA was given at 20 mg/d for 75 d followed by weekly doses of 50 mg, with the result that 99.9% of the subjects had sperm concentrations reduced to c 4 million/mL.[12] More intensive human clinical studies indicated that sperm motility was first markedly reduced and this was followed by reduced sperm numbers.”[10]

“In China, long-term clinical usage of GAA (gossypol acetic acid) for women treated for endometriosis, uterine myomas, and functional uterine bleeding has resulted in amenorrhea and atrophy of uteri. Zhu et al. (1984)[13] concluded from electron microscopic examination of uterine biopsies obtained from women that GAA had a locally cytotoxic effect on the uterus, in addition to a systemic effect via ovarian function.”[10]

“In summary, published data for female nonruminants indicate that GAA interferes with the expression of normal estrous cycles. Administration of GAA before implantation will inhibit pregnancy. Embryo survival also seems to be a potential problem. Possible mechanisms responsible for these effects of GAA include endocrine imbalance. Data largely support an effect of GAA on ovarian hormone secretion; however, a direct cytotoxic effect on the uterus or embryo cannot be excluded. In fact, some data substantially support the latter mechanism.”[10]

“The effect of gossypol acetic acid an cottonseed oil emulsion on human spermatozoal motility was tested. Contrary to a recent report [Waller et al. (1980): Contraception 22:183-187] that gossypol acetic acid is harmless to human spermatozoal motility in vitro, 10-3 M gossypol acetic acid completely abolished spermatozoal motility. This discrepancy might have stemmed from an oversight in the gossypol solubility. Cottonseed oil emulsion also exhibited spermatozoal motility inhibition. The applicability of this natural low toxicity cottonseed oil as vaginal contraceptive was explored.”[14]

“The irreversible effects of gossypol on male fertility have been well documented, as has the incidence of hypokalemia.”[15, 16]

“Further trials tested gossypol as a contraceptive agent for men at lower doses enrolling 151 men from various ethnic origins (Brazil, Nigeria, Kenya, and China) which received 15 mg racemic gossypol/day (0.24 mg/kg b.w. per day) for 12 or 16 weeks and 51 control subjects. Subjects were then randomized to either 7.5 or 10 mg/day corresponding to 0.12 and 0.17 mg/kg b.w. per day for further 40 weeks. Spermatogenesis suppression was attained in 81 of the 151 treated subjects and only one subject discontinued treatment (because of tiredness). Potassium levels fluctuated within the normal range, follicle stimulating hormone (FSH) levels increased consistently (indicative of reduced secretion of inhibin from Sertoli cells in the testes), testicular volume decreased, but after discontinuation values returned to control levels. Fifty one percent of the subjects who received 0.12 and 0.17 mg/kg b.w. per day recovered sperm counts to 20 million/mL within 12 months of discontinuing gossypol treatment. However, 18 percent of the remaining 48 patients were still azoospermic one year after termination of gossypol treatment. All men diagnosed with varicocele failed to reverse spermatogenesis suppression. Gossypol blood levels indicated that sperm suppression occurs independently of concentration, whereas spermatogenesis recovery appears to be concentration-dependent[17].”[18]

Gossypol Testing After Refining – A False Sense of Security

“The level of gossypol in crude solvent-extracted oil is 0.05–0.42%, and in crude screw-pressed oil 0.25–0.47% (2). Although almost all gossypol is removed during refining (3) to prevent the risk of toxicity, a sufficient amount remains to affect the keeping quality of the oil: The rate of darkening in the bleached oil is directly proportional to its gossypol content as well as to the time and temperature of storage (4). Historically, there has been little concern over gossypol in cottonseed oil, but interest in it has been spurred by its recent implication as a fertility control agent (5). A breakthrough of sorts in the production of stable-color oil and high-quality meal was made with the introduction of glandless cotton (6). Unfortunately, without gossypol, cotton is also more susceptible to pests, and glandless cotton has not been wholly accepted for planting. Because the oil produced from glandless cottonseed may still have some glands containing gossypol, it must be analyzed for its gossypol content. With the current high quality of refined oil, the method for determining gossypol developed by Yabe et al. (7) is being used at its lower limit, and gossypol often is not detectable. Other methods of analysis have been tried in a search for greater sensitivity, for example, HPLC (8). Nomeir and AbouDonia (9) reported on the qualitative and quantitative analysis of gossypol by HPLC and its stability in various solvents. AOCS (10) has adopted methods for determining free and total gossypol that use a spectrophotometer or colorimeter equipped with a filter for maximal transmittance at 440–460 nm. FTIR spectroscopy has been used for measurement of moisture content and iodine value in palm oil (11,12). In conjunction with chemometric techniques, FTIR data can be used to quantify, classify, and enumerate the differences between samples(13). In this work FTIR spectroscopy has been used to determine gossypol in cottonseed oil.”[11]

Various methods exist for testing the gossypol content in cottonseed, oil, press-cake and meal and they vary in sensitivity. “These methods include gravimetric, volumetric, colorimetric, spectrophotometric, polarographic, and luminescent means.”[15]

The actual amount of gossypol may be a higher than testing shows depending on the sensitivity of the testing method.[11] “However, it is found that the total amount of gossypol determined by HPLC is not always correlated with the results from the AOCS official methods. This phenomenon is ascribed to shortcomings of the AOCS official methods that depend on the aldehydic groups of all the gossypol and gossypol derivatives, which can lead to false readings resulting from the presence of nongossypol aldehydic-containing compounds that can also react with the dye reagent (Stipanovic et al., 1984). Additionally, the AOCS methods are often criticized for their laborious and time-consuming procedures as well as lack of analytical sensitivity and accuracy.”[15]

The FDA requires cottonseed for human consumption to have a, “Free gossypol content not to exceed 450 parts per million.”[19] However, the method required to measure the gossypol content of cottonseed oil is not specified by the FDA and most likely at the discretion of the manufacturer. This is important as certain effects of gossypol have occurred independently of concentration.

“Gossypol is chemically reactive due to the reactivity of carbonyl and phenolic hydroxyl groups as well as its bulky binaphthalene structure. Gossypol can react with other compounds to form bound gossypol (BG). In order to better describe the chemical status (forms) of gossypol in cottonseed products, three terms (i.e., FG, BG, and TG) are frequently used. Based on the AOCS (American Oil Chemists Society) official definition, FG is defined as gossypol and gossypol derivatives in cottonseed products that can be extracted by 70% aqueous acetone (AOCS, Ba 7-58). BG, formed during cottonseed processing by reaction of gossypol with other compounds, is not soluble in aqueous acetone. TG is defined as gossypol and gossypol derivatives, both FG and BG, which can react with 3-amino-1-propanol in dimethylformamide solution (AOCS, Ba 8-78). However, since the AOCS method (AOCS, Ba 8-78) only measures gossypol, gossypol analogs, and gossypol derivatives that have an available aldehyde moiety for the derivatization reaction, a fraction of gossypol derivatives that are unable to undergo this reaction will be excluded from the TG value. Regardless of the aforementioned shortcomings, FG and TG are still determined empirically, and BG is determined mathematically by the equation BG = TG - FG.”[15]

“It is arguable whether FG content is a good predictor of the toxicity of the cottonseed products (Calhoun, 1996; Calhoun et al., 1990a; Eagle and Davies, 1958; Eagle et al., 1956) because measurements of BG, FG, and TG are insufficient. For example, the BG fraction is not always entirely inactive depending on the mechanism(s) of gossypol binding that occurs during the cottonseed processing, the type of animals consuming the gossypol, and the physical form of the feed. Moreover, different gossypol derivatives also yield different physiological activities, and the (þ/)- two gossypol enantiomers, possess different biological activities. Study of the gossypol enantiomers revealed that only ()-gossypol was toxic to humans, but different ratios of (þ)- and ()-gossypol enantiomers in cotton plants did not affect the toxicity toward insects and pathogens (Liu et al., 2008). Calhoun (1996) suggested that different forms of BG might have different stabilities in vitro and in vivo, possibly because different cottonseed processing conditions favor various forms of BG. The animals selected for bioactivity experiments would also affect the results because of differing digestive environments. Therefore, current results related to the relationship between the available gossypol and its toxicity must be evaluated and interpreted carefully. Also, it should take into account of other factors such as dose and route of administration, the possibility of other toxic materials, and the degree of inactivation of administered gossypol before and/or after administration by reaction with components of the diet (Yu, 1987).”[15]

“The second “major problem” with cottonseeds, according to Swern, is the occurrence of aflatoxins resulting from infection with the Aspergillus flavus mold. The International Agency for Research on Cancer (IARC) categorized aflatoxins as group 1 agents, “carcinogenic to humans” (IARC 1976, 1987). Epidemiological studies noted “positive correlation between esti- mated aflatoxins intake or level of aflatoxin contamination of market food samples and cooked food and incidence of hepatocellular cancer.” The observations were supported by positive results in laboratory carcinogenicity and mutagenicity studies. Swern noted that with proper growing and storage conditions, and extraction and refining of the oil, the problems of aflatoxins and/or gossypol (the first “major problem”) were not “especially serious with refined cottonseed oil” (Swern 1979).”[20] However, the FDA has no requirement of aflatoxin testing of cottonseed oil or its products for human consumption.[19]

Cottonseed Oil Increases Cancer Risk

Cottonseed oil is considered an ‘equivocal carcinogen’ by the Registry of the Toxic Effects of Chemical Substances (RTECS) criteria and may be a co-carcinogen.[21] There is no difference noted for crude and refined cottonseed oil. Cotton is not classified as a food crop and farmers are allowed to use numerous pesticides when growing it. According to “Waking the Warrior Goddess: Dr. Christine Horner's Program to Protect Against and Fight Breast Cancer,” cotton farming accounts for up to one-third of all pesticide and uses more pesticides than on any other crop worldwide. The book “Chemistry and World Food Supplies,” advises that pesticides have the potential to be carcinogenic.

At minimum, if cotton products are going to be continued to be consumed in foods and medicine, it’s pesticide status and allowance should be changed to a food crop.

No well-documented solid scientific evidence currently exists describing any rigorous full-scale standard cancer bioassays of gossypol in animal models or any epidemiological findings of long-term exposure to humans.

The Problem with Vegetable & Seed Oils

For the past 4 decades, researchers have provided compelling evidence that processed vegetable and seed oils (trans fats) are most likely causing disease, growth defects and premature death.[22, 23] The best evidence suggests vegetable and seed oils, not animal or fruit fats, deserve the blame for increasing the risk for coronary artery disease, fat around the abdominal organs, insulin resistance and type-2 diabetes.[24] Unfortunately, it was not until June 2015, the FDA ruled to revoke the “generally recognized as safe” status to act as a ban for partially hydrogenated vegetable and seed oils.[25] We only heard that trans fats from vegetable and seed oils might be bad for our health after European countries outlawed trans fats. Scientific discoveries incompatible with commercial interests have a difficult time resulting in actionable changes. Make no mistake about it, vegetable and seed oils are heat-sensitive and processing them turns them into toxic, blood flow disrupting, pro-inflammatory trans fats.[26-28]

How Important Is It to Avoid Vegetable Oils?

Consuming adequate amounts of healthy fats is extremely important to be healthy. Research conducted at Harvard University showed omega-3 fatty acid deficiency is the 6th highest dietary cause of death in America, estimated to claim the lives of about 96,000 people each year.[29] Multiple sources suggest that human beings are healthiest with a ratio of omega-6 to omega-3 of 1:1, although Western diets are typically 15:1 to 16.7:1. “Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today's Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a low omega-6/omega-3 ratio) exert suppressive effects.”[30]

Good fats for humans: animal fats (beef tallow, duck fat, fish oil, pork lard); avocado oil; coconut butter, manna, milk or oil; macadamia nut oil (not used for cooking); olive oil; palm oil and walnut oil (not used for cooking).

Bad fats for humans: butter, canola oil, corn oil, cottonseed oil, flaxseed oil, grapeseed oil, peanut oil (not a true nut, but a legume that contains anti-nutrients), safflower oil, soy or soybean oil, sunflower seed oil, wheat germ oil, non-butter spreads (including margarine) and the so-called trans-free spreads.

Refined Cottonseed Oil Is a Drug

Although cottonseed oil is included in the FDA Inactive Ingredients Database (IM injections, oral, capsule, tablet and sublingual preparations), data directly demonstrates it is not inactive for human consumption or injection.

The definition of drug in English: A medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body.[31] Cottonseed oil and gossypol have shown antifeeding, toxicity, antifertility, anticancer, antivirus, antiparasitic, antimicrobial and plasma cholesterol lowering activities.[15]

Drug Warnings

Human clinical trials have reported the following adverse effects of gossypol emesis, xerostomia, transient transaminitis, dry skin, fatigue, nausea, transient ileus, minor hair thinning, mild thrombocytopenia, hypokalemia, grade 2 hepatic toxicity, peripheral edema, altered taste sensation and diarrhea.[15]

“Cottonseed oil emulsions have in the past been used in long-term intravenous nutrition regimens. A complex of adverse reactions, called the ‘overloading syndrome’, has been seen with chronic administration of cottonseed oil emulsion. This consisted of anorexia, nausea, abdominal pain, headache, fever, and sore throat. Signs of impaired liver function, anemia, hepatosplenomegaly, thrombocytopenia, and spontaneous hemorrhage due to delayed blood clotting have been reported. For parenteral nutrition purposes, cottonseed oil has been replaced by soybean oil, especially in pregnant women, where the use of cottonseed lipid emulsion has been associated with adverse effects.”[32, 33]

“A notable difference between the cottonseed oil emulsion and the soybean oil emulsion is the particle size. The cottonseed oil emulsion has much larger particles than the soybean oil emulsion. These larger particles may have been handled differently by the body, thus perhaps accounting for some of the toxic reactions.”[32, 33]

A Potential Cancer Drug

The apoptotic ability and inhibition of growth activity of cottonseed oil and gossypol have been studied to use as anticancer drugs. “Gossypol is capable of inhibiting the growth of a variety of cell lines including breast, colon, prostate, and leukemia cells (Balci et al., 1999; Benz et al., 1990; Huang et al., 2006; Zhang et al., 2003).”[15]

Toxicity

“The most common toxic effect of gossypol was shown in the cardiac irregularity which caused the death of animals due to the prevention of the liberation of oxygen from oxyhemoglobin (Menaul, 1923). Generally, the toxicological doses of gossypol are classified into three levels, which are (1) acute doses causing circulatory failure, (2) subchronic doses causing pulmonary edema, and (3) chronic doses causing symptoms of ill health and malnutrition (Abou-Donia, 1976). However, the toxic doses could not be specifically defined because they depend on different animal models.”[15]

“Signs of gossypol toxicity are similar in all animals and include laboured breathing and anorexia. Acute toxicity has been shown in the heart, lung, liver, and blood cells, resulting in increased erythrocyte fragility. Post mortem findings include generalised oedema and congestion of lungs and liver, fluid-filled thoracic and peritoneal cavities, and degeneration of heart fibres.”[18] Humans are part of the animal kingdom.

Pattern Thinking

This unique list is based on pattern thinking[34] of conservative evolutionary-biology, Paleo principles[35]. Other doctors tend to evaluate the healthiness of fats for human consumption on a case by case basis. However, pattern thinking's underlying repeating pattern phenomenon enables significantly deeper insights into complex domains.[34] For example, why would all seed oils except flaxseed oil be harmful?[36] Vegetable and seed oils are prone to harmful oxidative damage because they are separated from the antioxidants in the whole plant or seed form during processing.[22, 23] In other words, don’t eat and inject synthetic candle and soap ingredients. Pattern thinking provides the most logical nutritional recommendations.

Manufacturer’s Response

Recommended High Heat Fat

For the purposes of cooking and pharmaceutical heating, it is best to choose fats that are able to resist heat related damage of oxidation. Saturated fats have no room for additional oxygen, but are typically semisolid at room temperature. Monounsaturated fats, such as olive or avocado oil, have room for only one oxygen molecule but must be heated to a high degree to oxidize. Olive oil is 74% monosaturated and has a 13:1 omega-6: omega-3 ratio with a smoke point of 207°C or 405°F. Avocado oil is 74% monosaturated and has a 12:1 omega-6: omega-3 ratio with a smoke point of 271°C or 520°F. Most cooking and pharmaceutical manufacturing can be performed at a temperature of 204°C or 400°F or less and makes olive and avocado oil the best candidates when oils are needed.

Cottonseed oil is 52% polyunsaturated, 18% monosaturated and has a 54:1 omega-6: omega-3 ratio with a smoke point of 216°C or 420°F.

Currently available alternatives to cottonseed oil from pharmaceutical manufacturers (503b) are sesame oil and grapeseed oil. However, these oils have much higher omega-6: omega-3 ratios. Sesame oil has a 42:1 omega-6: omega-3 ratio with a smoke point of is 177°C or 350°F. Grapeseed oil is 12% saturated, 17% monosaturated and has a 676:1 omega-6: omega-3 ratio with a smoke point of is 177°C or 350°F.

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