In addition to the possible mutagenic/carcinogenic effects, some of the aforementioned chemical compounds may have other negative effects, such as effects on mental state. First we will review direct causal effects and, later, some association studies that cannot prove a causal link. For example, polycyclic aromatic hydrocarbons, such as pyrene and benzo[a]pyrene, form in animal products cooked at high temperatures (e.g., grilling and frying). These chemicals can induce behavioral depression in experimental animals at doses that exceed those found in human food [
170
-
173
]. This effect may be due to changes in the level or metabolism of neurotransmitters in various regions of the brain [
174
,
175
]. Benzo[a]pyrene has also impaired short-term memory and learning in rats in experiments where doses of this chemical exceed those that are present in human food [
176
,
177
].
Elevated blood levels of cholesterol oxidation products (oxysterols) play a role in the pathogenesis of atherosclerosis [
178
,
179
]. The latter is a pathological process leading to the clogging of blood vessels that underlies many cardiovascular diseases. In test tube experiments, which do not reflect what happens after consumption of cooked animal products, oxysterols can induce death of some types of cells in the central nervous system [
180
]. This should not be a cause for alarm, since oxysterols are present at low levels in the circulation of healthy people and serve several biological functions.
Research shows that a heterocyclic amine called norharman [
155
] reduces activity level in laboratory mice and causes pathological changes in the brain characteristic of neurodegenerative diseases [
181
]. The dose of norharman in this experiment was higher than what humans can receive with food. Another chemical from the same class, harman [
129
], which can also be present in cooked animal products, is toxic to some types of nerve cells [
182
]. Again, this should not be a cause for alarm, since both harman and norharman are present at low levels in the circulation of healthy people and serve several biological functions [
183
].
Other studies are less conclusive. Some of these studies have shown that chemicals formed by cooking may have something to do with abnormal mental functioning. But there is no proof that these compounds can
cause
such problems. For example, the blood level of creatinine increases after ingestion of cooked meat [
130
,
184
] but remains unchanged after ingestion of uncooked meat [
130
]. Elevated blood levels of creatinine and poor clearance of creatinine by the kidneys correlate with fatigue [
185
-
187
] and depressive symptoms in various groups of patients [
188
-
191
]. It is unknown if this relationship is coincidental or causal.
Elevated blood levels of creatinine and oxysterols correlate with cognitive impairment in various groups of patients [
192
-
195
]. Creatinine serves as an indicator of kidney dysfunction. Consequently, elevated blood levels of this chemical may point to accumulation of waste in blood due to insufficient kidney function. Thus, the reported cognitive impairment may be the result of kidney problems [
196
] rather than the elevated level of creatinine. Heterocyclic aromatic amines called harman and norharman [
129
] can cause toxicity for kidney cells [
197
,
198
], and the former can also be toxic to nerve cells [
182
,
199
,
200
]. The blood level of harman correlates with symptoms of anxiety and depression in alcoholics [
183
]. It is not known if this relationship is coincidental or causal.
To summarize, there is evidence that cooked meat can lower mood but no evidence that it can impair mental abilities. It is possible that the effects on mood are due to heterocyclic amines, but hard evidence is lacking. The above studies suggest that, from the standpoint of metabolism, humans should tolerate uncooked animal products better than cooked ones. The major obstacle is various pathogens that can be present in raw animal foods (
Table 1
).
Endnote B
describes possible technical approaches that can ensure the safety of such foods in the future.
The mere mention of raw animal products and food in the same sentence may seem unusual and unpleasant. Yet consumption of uncooked animal products is not as exotic as it appears at first glance [
201
,
202
]. Some types of sausage (such as salami and teewurst) are uncooked, that is, they undergo no thermal treatment [
201
,
203
]. There are also national/regional dishes that consist of raw animal foods, such as
sushi
(Japan),
hollandse nieuwe
(Netherlands), and
carne all’albese
(Piemonte, Italy). Consumption of raw ground beef is not uncommon in Belgium and some other European countries [
202
]. An even more vivid example is the traditional diet of indigenous ethnic groups of the Arctic region (for example, North American Eskimos). These peoples consume a large proportion of fish and meat (caribou, seal, walrus, polar bear, and whale) raw, frozen or thawed [
55
-
58
]. Meat and fish can constitute close to 100% of the Eskimo diet during the winter [
58
]. Nevertheless, at least in the United States and Russia, government regulators have not approved any raw animal products as safe for human consumption. Government regulators have neither banned nor approved foods such as sushi [
52
], whereas other food products such as raw dairy are either banned or face numerous restrictions on transportation and sales [
204
].
Going back to the effects of diets on metabolism, people should tolerate uncooked animal foods well if these foods are free of pathogens. This is because the raw diet is very old and pervasive in nature [
45
]. For example, animals in the wild do not cook their food [
45
]. Evolutionary predecessors as well as some early humans in all likelihood consumed a 100% raw food diet, prior to the mastery of cooking with fire approximately 300,000 years ago [
42
]. Some reports of successful control of fire, but not cooking, date as far back as 1.0 to 1.6 million years [
205
,
206
,
1004
]. Cooking with fire reduces the risk of infectious disease because it kills most pathogens [
139
], but it also produces chemical modifications in food, as we already discussed above. It is possible that during the last 300,000 years, the human immune system (at least in those living outside the Arctic region) has grown unaccustomed to the pathogens that occur in raw animal foods (
Table 1
). For this reason, these foods are not safe for human consumption. In addition, given humankind’s long history with cooking,
Homo sapiens
may have adapted to cooked food genetically through natural selection. Therefore, it is possible that humans need a certain percentage of cooked food in their diet for normal functioning.
Cooking has other benefits in addition to disinfection of food. For instance, cooked meat requires less energy to digest it than uncooked meat [
207
]. Cooking can also reduce the concentration of organic pollutants in animal products [
208
-
210
]. Finally, the negative effects of cooked high-protein diets [
110
-
114
] do not manifest themselves in people on cooked
protein-normal
diets. These data suggest that the liver detoxification system can neutralize the small amounts of novel chemicals that form in animal products during cooking.
It is now time to discuss chemicals formed by cooking of grains. These chemicals are absent in raw cereal grains. The chemical reaction between certain amino acids (components of proteins) and some types of sugars (components of carbohydrates, such as starch), when you mix and heat them, is called the Maillard reaction. Novel chemicals that form in the Maillard reaction are called
Maillard reaction products
. Cereal grains (e.g., wheat and rice) contain significant amounts of both protein and carbohydrates. Thus, cooking of grains leads to the formation of a number of different Maillard reaction products. The amount of Maillard reaction products increases with the temperature and duration of cooking. This means that boiled grains (moderate cooking temperature) contain smaller amounts of Maillard reaction products compared to bread (high cooking temperature) [
211
-
215
].
Some of the Maillard reaction products that science identified in cooked cereal grains are the following: acrylamide, carboxymethyllysine, carboxyethyllysine, and fructosyllysine [
216
-
219
]. Of these four, acrylamide is the only chemical with published evidence of
direct
negative effects on mental abilities [
220
]. With the other three, all studies are correlational, where a direct causal link is possible but not proven [
221
-
223
].
A number of studies have shown that acrylamide, which is also a well-known industrial pollutant, is toxic to neurons. It can have several adverse neuropsychiatric effects in humans and laboratory animals. This chemical received a lot of attention several years ago. Swedish researchers announced that crispbread and French fries contain the levels of acrylamide that exceed 500-fold the maximal level allowed in drinking water by the World Health Organization [
224
,
225
]. In contrast to bread, which undergoes cooking at high temperatures (300-400 degrees Celsius or 570-750°F), boiled grains contain undetectable levels of acrylamide [
215
,
225
]. Boiled grains may contain Maillard reaction products other than acrylamide [
212
-
214
]. Table 2 below summarizes the acrylamide content of various types of cereal grains. It is worth mentioning that nobody has proven the hypothetical carcinogenic effects of acrylamide in humans [
220
].
Table 2.
Acrylamide content of various types of grains [
211
,
215
,
225
,
235
]. “Undetectable” means below detection level of available analytical methods. N/A means data are not available. The neurotoxic dose of acrylamide is 200-500 micrograms per kilogram of body weight per day [
220
,
227
].
----------------------------------
Soaked raw grains or water extract of raw whole-grain flour
Acrylamide content
:
undetectable (< 5 mcg/kg)
Can this food deliver a neurotoxic dose?
No
Effects* on mental abilities
:
increased alertness
Boiled whole grains
Acrylamide content
:
undetectable (< 5 mcg/kg)
Can this food deliver a neurotoxic dose?
No
Effects* on mental abilities
:
slowing; reduced impulsivity
Breakfast cereals
Acrylamide content
:
~60 mcg/kg
Can this food deliver a neurotoxic dose?
No